A Review of Neuroreceptors for Clinical and Experimental Neuropharmacology
in Central Nervous System Disorders

Susan   C.   McKarns
doi:10.2174/2772432817666220301104118
Abstract

The neurobiology drug discovery landscape has transformed over the past decade or so by the discovery of allosteric modulators of receptor superfamilies. A wide range of physiological reactions can occur in response to a limited number of neurotransmitters. This review provides an update on physiological features of the receptors and the signaling pathways that are generated in response to neuroreceptor activation that allow the explanation of this vast array of neurotransmitter responses. Primarily based upon structure, receptors in the nervous system can be classified into four groups: Gprotein coupled receptors, ligand-gated receptors, enzyme-linked receptors, and nuclear receptors. With a particular emphasis on the central nervous system, i.e., brain, spinal cord, and optic nerves, we identify the neuroreceptors, their endogenous agonists, antagonists, sites of expression within the nervous system, current neuropharmacological clinical use, and potential for new drug discovery. New molecular approaches and advances in our knowledge of neuronal communication in processes involved in development, functioning and disorders of the nervous system combined with opportunities to re-purpose existing drugs for new indications continue to highlight the exciting opportunities to improve human health.
Keywords: Neuroreceptor, central nervous system, drug discovery, environmental stimuli, ion channels, G protein-coupled receptors, enzyme-linked receptors, nuclear receptors, endogenous ligands, signaling cascades.
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[1]
Micheva KD, Busse B, Weiler NC, O’Rourke N, Smith SJ. Single-synapse analysis of a diverse synapse population: Proteomic imaging methods and markers. Neuron  2010; 68(4): 639-53.
 [http://dx.doi.org/10.1016/j.neuron.2010.09.024] [PMID: 21092855]

[2]
Lovinger DM. Communication networks in the brain: Neurons, receptors, neurotransmitters, and alcohol. Alcohol Res Health  2008; 31(3): 196-214.
 [PMID: 23584863]

[3]
Chiu AM, Wang J, Fiske MP, et al. NMDAR-activated PP1 dephosphorylates GluN2B to modulate NMDAR synaptic content. Cell Rep  2019; 28(2): 332-41.
 [http://dx.doi.org/10.1016/j.celrep.2019.06.030] [PMID: 31291571]

[4]
Yang D, Zhou Q, Labroska V, et al. G protein-coupled receptors: Structure- and function-based drug discovery. Signal Transduct Target Ther  2021; 6(1): 7.
 [http://dx.doi.org/10.1038/s41392-020-00435-w] [PMID: 33414387]

[5]
Azam S, Haque ME, Jakaria M, Jo SH, Kim IS, Choi DK. G-protein-coupled receptors in CNS: A potential therapeutic target for intervention in neurodegenerative disorders and associated cognitive deficits. Cells  2020; 9(2): 506.
 [http://dx.doi.org/10.3390/cells9020506] [PMID: 32102186]

[6]
Zhang X, Chen WW, Huang WJ. Ligand gated channels in nervous system. J Neurosurg Sci  2019; 63(4): 493-4.
 [http://dx.doi.org/10.23736/S0390-5616.17.04021-8] [PMID: 29115097]

[7]
Nemecz Á, Prevost MS, Menny A, Corringer PJ. Emerging molecular mechanisms of signal transduction in pentameric ligand-gated ion channels. Neuron  2016; 90(3): 452-70.
 [http://dx.doi.org/10.1016/j.neuron.2016.03.032] [PMID: 27151638]

[8]
Bowie D. Ligand-gated ion channels: From genes to behaviour. J Physiol  2012; 590(1): 9-11.
 [http://dx.doi.org/10.1113/jphysiol.2011.224592] [PMID: 22210286]

[9]
Rosenbaum DM, Cherezov V, Hanson MA, et al. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science  2007; 318(5854): 1266-73.
 [http://dx.doi.org/10.1126/science.1150609] [PMID: 17962519]

[10]
Cherezov V, Rosenbaum DM, Hanson MA, et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science  2007; 318(5854): 1258-65.
 [http://dx.doi.org/10.1126/science.1150577] [PMID: 17962520]

[11]
Hyman SE. Neurotransmitters. Curr Biol  2005; 15(5): R154-8.
 [http://dx.doi.org/10.1016/j.cub.2005.02.037] [PMID: 15753022]

[12]
Alexander SP, Benson HE, Faccenda E, et al. CGTP Collaborators. The concise guide to pharmacology 2013/14: Catalytic receptors. Br J Pharmacol  2013; 170(8): 1676-705.
 [http://dx.doi.org/10.1111/bph.12449] [PMID: 24528241]

[13]
Vigneswara V, Kundi S, Ahmed Z. Receptor tyrosine kinases: Molecular switches regulating CNS axon regeneration. J Signal Transduct  2012; 2012: 361721.
 [http://dx.doi.org/10.1155/2012/361721] [PMID: 22848811]

[14]
Olivares AM, Moreno-Ramos OA, Haider NB. Role of nuclear receptors in central nervous system development and associated diseases. J Exp Neurosci  2016; 9 (Suppl. 2): 93-121.
 [PMID: 27168725]

[15]
Xu D, Huang S, Wang H, Xie W. Regulation of brain drug metabolizing enzymes and transporters by nuclear receptors. Drug Metab Rev  2018; 50(4): 407-14.
 [http://dx.doi.org/10.1080/03602532.2018.1554673] [PMID: 30501435]

[16]
Santos R, Ursu O, Gaulton A, et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov  2017; 16(1): 19-34.
 [http://dx.doi.org/10.1038/nrd.2016.230] [PMID: 27910877]

[17]
Hammond-Weinberger DR, Wang Y, Glavis-Bloom A, Spitzer NC. Mechanism for neurotransmitter-receptor matching. Proc Natl Acad Sci USA  2020; 117(8): 4368-74.
 [http://dx.doi.org/10.1073/pnas.1916600117] [PMID: 32041885]

[18]
Acher FC, Cabayé A, Eshak F, Goupil-Lamy A, Pin JP. Metabotropic glutamate receptor orthosteric ligands and their binding sites. Neuropharmacology  2022; 204: 108886.
 [http://dx.doi.org/10.1016/j.neuropharm.2021.108886] [PMID: 34813860]

[19]
Reddy VB, Sun S, Azimi E, Elmariah SB, Dong X, Lerner EA. Redefining the concept of protease-activated receptors: Cathepsin S evokes itch via activation of Mrgprs. Nat Commun  2015; 6(1): 7864.
 [http://dx.doi.org/10.1038/ncomms8864] [PMID: 26216096]

[20]
Rajkumar P, Aisenberg WH, Acres OW, Protzko RJ, Pluznick JL. Identification and characterization of novel renal sensory receptors. PLoS One  2014; 9(10): e111053.
 [http://dx.doi.org/10.1371/journal.pone.0111053] [PMID: 25340336]

[21]
Paradiso K, Brehm P. Long-term desensitization of nicotinic acetylcholine receptors is regulated via protein kinase A-mediated phosphorylation. J Neurosci  1998; 18(22): 9227-37.
 [http://dx.doi.org/10.1523/JNEUROSCI.18-22-09227.1998] [PMID: 9801362]

[22]
Pugh JR, Raman IM. GABAA receptor kinetics in the cerebellar nuclei: Evidence for detection of transmitter from distant release sites. Biophys J  2005; 88(3): 1740-54.
 [http://dx.doi.org/10.1529/biophysj.104.055814] [PMID: 15626699]

[23]
Papke D, Gonzalez-Gutierrez G, Grosman C. Desensitization of neurotransmitter-gated ion channels during high-frequency stimulation: A comparative study of Cys-loop, AMPA and purinergic receptors. J Physiol  2011; 589(Pt 7): 1571-85.
 [http://dx.doi.org/10.1113/jphysiol.2010.203315] [PMID: 21300749]

[24]
Chen JF, Eltzschig HK, Fredholm BB. Adenosine receptors as drug targets--what are the challenges? Nat Rev Drug Discov  2013; 12(4): 265-86.
 [http://dx.doi.org/10.1038/nrd3955] [PMID: 23535933]

[25]
Reidenberg MM. Drug discontinuation effects are part of the pharmacology of a drug. J Pharmacol Exp Ther  2011; 339(2): 324-8.
 [http://dx.doi.org/10.1124/jpet.111.183285] [PMID: 21849624]

[26]
Rosenbaum MI, Clemmensen LS, Bredt DS, Bettler B, Strømgaard K. Targeting receptor complexes: A new dimension in drug discovery. Nat Rev Drug Discov  2020; 19(12): 884-901.
 [http://dx.doi.org/10.1038/s41573-020-0086-4] [PMID: 33177699]

[27]
Harding SD, Sharman JL, Faccenda E, et al. NC-IUPHAR. The IUPHAR/BPS guide to pharmacology in 2018: Updates and expansion to encompass the new guide to immunopharmacology. Nucleic Acids Res  2018; 46(D1): D1091-106.
 [http://dx.doi.org/10.1093/nar/gkx1121] [PMID: 29149325]

[28]
Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: New agents, targets and indications. Nat Rev Drug Discov  2017; 16(12): 829-42.
 [http://dx.doi.org/10.1038/nrd.2017.178] [PMID: 29075003]

[29]
Huang Y, Todd N, Thathiah A. The role of GPCRs in neurodegenerative diseases: Avenues for therapeutic intervention. Curr Opin Pharmacol  2017; 32: 96-110.
 [http://dx.doi.org/10.1016/j.coph.2017.02.001] [PMID: 28288370]

[30]
Insel PA, Sriram K, Gorr MW, et al. GPCRomics: An approach to discover GPCR drug targets. Trends Pharmacol Sci  2019; 40(6): 378-87.
 [http://dx.doi.org/10.1016/j.tips.2019.04.001] [PMID: 31078319]

[31]
Sriram K, Insel PA. G protein-coupled receptors as targets for approved drugs: How many targets and how many drugs? Mol Pharmacol  2018; 93(4): 251-8.
 [http://dx.doi.org/10.1124/mol.117.111062] [PMID: 29298813]

[32]
van Gastel J, Leysen H, Boddaert J, et al. Aging-related modifications to G protein-coupled receptor signaling diversity. Pharmacol Ther  2021; 223: 107793.
 [http://dx.doi.org/10.1016/j.pharmthera.2020.107793] [PMID: 33316288]

[33]
Santos-Otte P, Leysen H, van Gastel J, Hendrickx JO, Martin B, Maudsley SG. Protein-coupled receptor systems and their role in cellular senescence. Comput Struct Biotechnol J  2019; 17: 1265-77.
 [http://dx.doi.org/10.1016/j.csbj.2019.08.005] [PMID: 31921393]

[34]
de Oliveira PG, Ramos MLS, Amaro AJ, Dias RA, Vieira SI. Gi/o-Protein coupled receptors in the aging brain. Front Aging Neurosci  2019; 11: 89.
 [http://dx.doi.org/10.3389/fnagi.2019.00089] [PMID: 31105551]

[35]
Wootten D, Christopoulos A, Marti-Solano M, Babu MM, Sexton PM. Mechanisms of signalling and biased agonism in G protein-coupled receptors. Nat Rev Mol Cell Biol  2018; 19(10): 638-53.
 [http://dx.doi.org/10.1038/s41580-018-0049-3] [PMID: 30104700]

[36]
Smith JS, Lefkowitz RJ, Rajagopal S. Biased signalling: From simple switches to allosteric microprocessors. Nat Rev Drug Discov  2018; 17(4): 243-60.
 [http://dx.doi.org/10.1038/nrd.2017.229] [PMID: 29302067]

[37]
Guerram M, Zhang LY, Jiang ZZ. G-protein coupled receptors as therapeutic targets for neurodegenerative and cerebrovascular diseases. Neurochem Int  2016; 101: 1-14.
 [http://dx.doi.org/10.1016/j.neuint.2016.09.005] [PMID: 27620813]

[38]
DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: Correlation with cognitive severity. Ann Neurol  1990; 27(5): 457-64.
 [http://dx.doi.org/10.1002/ana.410270502] [PMID: 2360787]

[39]
Johnson ECB, Dammer EB, Duong DM, et al. Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nat Med  2020; 26(5): 769-80.
 [http://dx.doi.org/10.1038/s41591-020-0815-6] [PMID: 32284590]

[40]
Wingo AP, Dammer EB, Breen MS, et al. Large-scale proteomic analysis of human brain identifies proteins associated with cognitive trajectory in advanced age. Nat Commun  2019; 10(1): 1619.
 [http://dx.doi.org/10.1038/s41467-019-09613-z] [PMID: 30962425]

[41]
Perez-Nievas BG, Stein TD, Tai HC, et al. Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology. Brain  2013; 136(Pt 8): 2510-26.
 [http://dx.doi.org/10.1093/brain/awt171] [PMID: 23824488]

[42]
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med  2011; 1(1): a006189.
 [http://dx.doi.org/10.1101/cshperspect.a006189] [PMID: 22229116]

[43]
Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: Pharmacology and toxicology. Curr Neuropharmacol  2013; 11(3): 315-35.
 [http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]

[44]
Selkoe DJ. The therapeutics of Alzheimer’s disease: Where we stand and where we are heading. Ann Neurol  2013; 74(3): 328-36.
 [http://dx.doi.org/10.1002/ana.24001] [PMID: 25813842]

[45]
Grossberg GT, Farlow MR, Meng X, Velting DM. Evaluating high-dose rivastigmine patch in severe Alzheimer’s disease: Analyses with concomitant memantine usage as a factor. Curr Alzheimer Res  2015; 12(1): 53-60.
 [http://dx.doi.org/10.2174/1567205011666141218122835] [PMID: 25523430]

[46]
Farlow MR, Graham SM, Alva G. Memantine for the treatment of Alzheimer’s disease: Tolerability and safety data from clinical trials. Drug Saf  2008; 31(7): 577-85.
 [http://dx.doi.org/10.2165/00002018-200831070-00003] [PMID: 18558791]

[47]
Zhang G, Ásgeirsdóttir HN, Cohen SJ, Munchow AH, Barrera MP, Stackman RW Jr. Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice. Neuropharmacology  2013; 64: 403-13.
 [http://dx.doi.org/10.1016/j.neuropharm.2012.06.007] [PMID: 22722027]

[48]
Lo AC, De Maeyer JH, Vermaercke B, Callaerts-Vegh Z, Schuurkes JA, D’Hooge R. SSP-002392, a new 5-HT4 receptor agonist, dose-dependently reverses scopolamine-induced learning and memory impairments in C57Bl/6 mice. Neuropharmacology  2014; 85: 178-89.
 [http://dx.doi.org/10.1016/j.neuropharm.2014.05.013] [PMID: 24863046]

[49]
Hamilton A, Esseltine JL, DeVries RA, Cregan SP, Ferguson SS. Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer’s disease. Mol Brain  2014; 7(1): 40.
 [http://dx.doi.org/10.1186/1756-6606-7-40] [PMID: 24886239]

[50]
Guimarães TR, Swanson E, Kofler J, Thathiah A. G protein-coupled receptor kinases are associated with Alzheimer’s disease pathology. Neuropathol Appl Neurobiol  2021; 47(7): 942-57.
 [http://dx.doi.org/10.1111/nan.12742] [PMID: 34164834]

[51]
Cenci MA, Lundblad M. Post- versus presynaptic plasticity in L-DOPA-induced dyskinesia. J Neurochem  2006; 99(2): 381-92.
 [http://dx.doi.org/10.1111/j.1471-4159.2006.04124.x] [PMID: 16942598]

[52]
Seeman P, Niznik HB. Dopamine receptors and transporters in Parkinson’s disease and schizophrenia. FASEB J  1990; 4(10): 2737-44.
 [http://dx.doi.org/10.1096/fasebj.4.10.2197154] [PMID: 2197154]

[53]
Galantucci S, Agosta F, Stefanova E, et al. Structural brain connectome and cognitive impairment in Parkinson disease. Radiology  2017; 283(2): 515-25.
 [http://dx.doi.org/10.1148/radiol.2016160274] [PMID: 27924721]

[54]
Iarkov A, Mendoza C, Echeverria V. Cholinergic receptor modulation as a target for preventing dementia in Parkinson’s disease. Front Neurosci  2021; 15: 665820.
 [http://dx.doi.org/10.3389/fnins.2021.665820] [PMID: 34616271]

[55]
Stacy M, Galbreath A. Optimizing long-term therapy for Parkinson disease: Levodopa, dopamine agonists, and treatment-associated dyskinesia. Clin Neuropharmacol  2008; 31(1): 51-6.
 [http://dx.doi.org/10.1097/WNF.0b013e318065b088] [PMID: 18303491]

[56]
Stacy M, Galbreath A. Optimizing long-term therapy for Parkinson disease: Options for treatment-associated dyskinesia. Clin Neuropharmacol  2008; 31(2): 120-5.
 [http://dx.doi.org/10.1097/WNF.0b013e318065b09c] [PMID: 18382184]

[57]
Komatsu H. Innovative therapeutic approaches for Huntington’s disease: From nucleic acids to GPCR-targeting small molecules. Front Cell Neurosci  2021; 15: 785703.
 [http://dx.doi.org/10.3389/fncel.2021.785703] [PMID: 34899193]

[58]
Beal MF, Ferrante RJ, Swartz KJ, Kowall NW. Chronic quinolinic acid lesions in rats closely resemble Huntington’s disease. J Neurosci  1991; 11(6): 1649-59.
 [http://dx.doi.org/10.1523/JNEUROSCI.11-06-01649.1991] [PMID: 1710657]

[59]
Bruno V, Ksiazek I, Battaglia G, et al. Selective blockade of metabotropic glutamate receptor subtype 5 is neuroprotective. Neuropharmacology  2000; 39(12): 2223-30.
 [http://dx.doi.org/10.1016/S0028-3908(00)00079-4] [PMID: 10974306]

[60]
Charvin D, Vanhoutte P, Pagès C, Borrelli E, Caboche J. Unraveling a role for dopamine in Huntington’s disease: The dual role of reactive oxygen species and D2 receptor stimulation. Proc Natl Acad Sci USA  2005; 102(34): 12218-23.
 [http://dx.doi.org/10.1073/pnas.0502698102] [PMID: 16103364]

[61]
Chen JY, Wang EA, Cepeda C, Levine MS. Dopamine imbalance in Huntington’s disease: A mechanism for the lack of behavioral flexibility. Front Neurosci  2013; 7: 114.
 [http://dx.doi.org/10.3389/fnins.2013.00114] [PMID: 23847463]

[62]
Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics  2006; 47(1): 70-2.
 [http://dx.doi.org/10.1176/appi.psy.47.1.70] [PMID: 16384811]

[63]
Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine’s antidepressant activity. Neuropsychopharmacology  2008; 33(10): 2303-12.
 [http://dx.doi.org/10.1038/sj.npp.1301646] [PMID: 18059438]

[64]
Komatsu H, Maruyama M, Yao S, et al. Anatomical transcriptome of G protein-coupled receptors leads to the identification of a novel therapeutic candidate GPR52 for psychiatric disorders. PLoS One  2014; 9(2): e90134.
 [http://dx.doi.org/10.1371/journal.pone.0090134] [PMID: 24587241]

[65]
Alexander SP, Davenport AP, Kelly E, et al. CGTP Collaborators. The concise guide to pharmacology 2015/16 protein-coupled receptors. Br J Pharmacol  2015; 172(24): 5744-869.
 [http://dx.doi.org/10.1111/bph.13348] [PMID: 26650439]

[66]
Tse LH, Wong YH. GPCRs in autocrine and paracrine regulations. Front Endocrinol (Lausanne)  2019; 10: 428.
 [http://dx.doi.org/10.3389/fendo.2019.00428] [PMID: 31354618]

[67]
Huang Y, Thathiah A. Regulation of neuronal communication by G protein-coupled receptors. FEBS Lett  2015; 589(14): 1607-19.
 [http://dx.doi.org/10.1016/j.febslet.2015.05.007] [PMID: 25980603]

[68]
Maziarz M, Park JC, Leyme A, et al. Revealing the activity of trimeric G-proteins in live cells with a versatile biosensor design. Cell  2020; 182(3): 770-85.
 [http://dx.doi.org/10.1016/j.cell.2020.06.020] [PMID: 32634377]

[69]
Gurevich VV, Gurevich EV. GPCR signaling regulation: The role of GRKs and arrestins. Front Pharmacol  2019; 10: 125.
 [http://dx.doi.org/10.3389/fphar.2019.00125] [PMID: 30837883]

[70]
Gulati S, Jin H, Masuho I, et al. Targeting G protein-coupled receptor signaling at the G protein level with a selective nanobody inhibitor. Nat Commun  2018; 9(1): 1996.
 [http://dx.doi.org/10.1038/s41467-018-04432-0] [PMID: 29777099]

[71]
Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell  2008; 133(1): 38-52.
 [http://dx.doi.org/10.1016/j.cell.2008.03.011] [PMID: 18394988]

[72]
Rosenbaum DM, Rasmussen SG, Kobilka BK. The structure and function of G-protein-coupled receptors. Nature  2009; 459(7245): 356-63.
 [http://dx.doi.org/10.1038/nature08144] [PMID: 19458711]

[73]
Oldham WM, Hamm HE. Heterotrimeric G protein activation by G-protein-coupled receptors. Nat Rev Mol Cell Biol  2008; 9(1): 60-71.
 [http://dx.doi.org/10.1038/nrm2299] [PMID: 18043707]

[74]
Marshall FH. Heterodimerization of G-protein-coupled receptors in the CNS. Curr Opin Pharmacol  2001; 1(1): 40-4.
 [http://dx.doi.org/10.1016/S1471-4892(01)00001-7] [PMID: 11712533]

[75]
Husted AS, Trauelsen M, Rudenko O, Hjorth SA, Schwartz TW. GPCR-mediated signaling of metabolites. Cell Metab  2017; 25(4): 777-96.
 [http://dx.doi.org/10.1016/j.cmet.2017.03.008] [PMID: 28380372]

[76]
Syrovatkina V, Alegre KO, Dey R, Huang XY. Regulation, signaling, and physiological functions of G-proteins. J Mol Biol  2016; 428(19): 3850-68.
 [http://dx.doi.org/10.1016/j.jmb.2016.08.002] [PMID: 27515397]

[77]
Eichel K, von Zastrow M. Subcellular organization of GPCR signaling. Trends Pharmacol Sci  2018; 39(2): 200-8.
 [http://dx.doi.org/10.1016/j.tips.2017.11.009] [PMID: 29478570]

[78]
Alexander SPH, Christopoulos A, Davenport AP, et al. CGTP Collaborators. The concise guide to pharmacology 2019/20: G protein-coupled receptors. Br J Pharmacol  2019; 176 (Suppl. 1): S21-S141.
 [http://dx.doi.org/10.1111/bph.14748] [PMID: 31710717]

[79]
Civelli O, Reinscheid RK, Zhang Y, Wang Z, Fredriksson R, Schiöth HB. G protein-coupled receptor deorphanizations. Annu Rev Pharmacol Toxicol  2013; 53(1): 127-46.
 [http://dx.doi.org/10.1146/annurev-pharmtox-010611-134548] [PMID: 23020293]

[80]
Sakmar TP, Menon ST, Marin EP, Awad ES. Rhodopsin: Insights from recent structural studies. Annu Rev Biophys Biomol Struct  2002; 31(1): 443-84.
 [http://dx.doi.org/10.1146/annurev.biophys.31.082901.134348] [PMID: 11988478]

[81]
Hollenstein K, de Graaf C, Bortolato A, Wang MW, Marshall FH, Stevens RC. Insights into the structure of class B GPCRs. Trends Pharmacol Sci  2014; 35(1): 12-22.
 [http://dx.doi.org/10.1016/j.tips.2013.11.001] [PMID: 24359917]

[82]
Bortolato A, Doré AS, Hollenstein K, Tehan BG, Mason JS, Marshall FH. Structure of class B GPCRs: New horizons for drug discovery. Br J Pharmacol  2014; 171(13): 3132-45.
 [http://dx.doi.org/10.1111/bph.12689] [PMID: 24628305]

[83]
Kypreos M, Banerjee T, Mukherjee D. G protein-coupled receptors--potential roles in clinical pharmacology. Cardiovasc Hematol Agents Med Chem  2014; 12(1): 29-33.
 [http://dx.doi.org/10.2174/187152571201141201093751] [PMID: 25470151]

[84]
Engers DW, Lindsley CW. Allosteric modulation of class C GPCRs: A novel approach for the treatment of CNS disorders. Drug Discov Today Technol  2013; 10(2): e269-76.
 [http://dx.doi.org/10.1016/j.ddtec.2012.10.007] [PMID: 24050278]

[85]
Jakubík J, El-Fakahany EE. Allosteric modulation of GPCRs of class a by cholesterol. Int J Mol Sci  2021; 22(4): 1953.
 [http://dx.doi.org/10.3390/ijms22041953] [PMID: 33669406]

[86]
Wold EA, Chen J, Cunningham KA, Zhou J. Allosteric modulation of class A GPCRs: Targets, agents, and emerging concepts. J Med Chem  2019; 62(1): 88-127.
 [http://dx.doi.org/10.1021/acs.jmedchem.8b00875] [PMID: 30106578]

[87]
Bjarnadóttir TK, Fredriksson R, Schiöth HB. The adhesion GPCRs: A unique family of G protein-coupled receptors with important roles in both central and peripheral tissues. Cell Mol Life Sci  2007; 64(16): 2104-19.
 [http://dx.doi.org/10.1007/s00018-007-7067-1] [PMID: 17502995]

[88]
Mehta P, Piao X. Adhesion G-protein coupled receptors and extracellular matrix proteins: Roles in myelination and glial cell development. Dev Dyn  2017; 246(4): 275-84.
 [http://dx.doi.org/10.1002/dvdy.24473] [PMID: 27859941]

[89]
Civelli O. Orphan GPCRs and neuromodulation. Neuron  2012; 76(1): 12-21.
 [http://dx.doi.org/10.1016/j.neuron.2012.09.009] [PMID: 23040803]

[90]
Alavi MS, Shamsizadeh A, Azhdari-Zarmehri H, Roohbakhsh A. Orphan G protein-coupled receptors: The role in CNS disorders. Biomed Pharmacother  2018; 98: 222-32.
 [http://dx.doi.org/10.1016/j.biopha.2017.12.056] [PMID: 29268243]

[91]
Watkins LR, Orlandi C. Orphan G protein coupled receptors in affective disorders. Genes (Basel)  2020; 11(6): 11.
 [http://dx.doi.org/10.3390/genes11060694] [PMID: 32599826]

[92]
Zhao M, Wang Z, Yang M, et al. The roles of orphan G protein-coupled receptors in autoimmune diseases. Clin Rev Allergy Immunol  2021; 60(2): 220-43.
 [http://dx.doi.org/10.1007/s12016-020-08829-y] [PMID: 33411320]

[93]
Allende G, Chávez-Reyes J, Guerrero-Alba R, Vázquez-León P, Marichal-Cancino BA. Advances in neurobiology and pharmacology of GPR12. Front Pharmacol  2020; 11: 628.
 [http://dx.doi.org/10.3389/fphar.2020.00628] [PMID: 32457622]

[94]
Mantas I, Yang Y, Mannoury-la-Cour C, Millan MJ, Zhang X, Svenningsson P. Genetic deletion of GPR88 enhances the locomotor response to L-DOPA in experimental parkinsonism while counteracting the induction of dyskinesia. Neuropharmacology  2020; 162: 107829.
 [http://dx.doi.org/10.1016/j.neuropharm.2019.107829] [PMID: 31666199]

[95]
Ye N, Li B, Mao Q, et al. Orphan receptor GPR88 as an emerging neurotherapeutic target. ACS Chem Neurosci  2019; 10(1): 190-200.
 [http://dx.doi.org/10.1021/acschemneuro.8b00572] [PMID: 30540906]

[96]
Cullen M, Elzarrad MK, Seaman S, et al. GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier. Proc Natl Acad Sci USA  2011; 108(14): 5759-64.
 [http://dx.doi.org/10.1073/pnas.1017192108] [PMID: 21421844]

[97]
Langosch D, Thomas L, Betz H. Conserved quaternary structure of ligand-gated ion channels: The postsynaptic glycine receptor is a pentamer. Proc Natl Acad Sci USA  1988; 85(19): 7394-8.
 [http://dx.doi.org/10.1073/pnas.85.19.7394] [PMID: 2459705]

[98]
Smart TG, Paoletti P. Synaptic neurotransmitter-gated receptors. Cold Spring Harb Perspect Biol  2012; 4(3): 4.
 [http://dx.doi.org/10.1101/cshperspect.a009662] [PMID: 22233560]

[99]
Kumar A, Basak S, Chakrapani S. Recombinant expression and purification of pentameric ligand-gated ion channels for Cryo-EM structural studies. Methods Enzymol  2021; 652: 81-103.
 [http://dx.doi.org/10.1016/bs.mie.2021.01.022] [PMID: 34059291]

[100]
Alexander SPH, Mathie A, Peters JA, et al. CGTP Collaborators. The concise guide to pharmacology 2019/20: Ion channels. Br J Pharmacol  2019; 176 (Suppl. 1): S142-228.
 [http://dx.doi.org/10.1111/bph.14749] [PMID: 31710715]

[101]
Cheng YR, Jiang BY, Chen CC. Acid-sensing ion channels: Dual function proteins for chemo-sensing and mechano-sensing. J Biomed Sci  2018; 25(1): 46.
 [http://dx.doi.org/10.1186/s12929-018-0448-y] [PMID: 29793480]

[102]
Feske S, Wulff H, Skolnik EY. Ion channels in innate and adaptive immunity. Annu Rev Immunol  2015; 33(1): 291-353.
 [http://dx.doi.org/10.1146/annurev-immunol-032414-112212] [PMID: 25861976]

[103]
Jin Z, Mendu SK, Birnir B. GABA is an effective immunomodulatory molecule. Amino Acids  2013; 45(1): 87-94.
 [http://dx.doi.org/10.1007/s00726-011-1193-7] [PMID: 22160261]

[104]
Kleopa KA. Autoimmune channelopathies of the nervous system. Curr Neuropharmacol  2011; 9(3): 458-67.
 [http://dx.doi.org/10.2174/157015911796557966] [PMID: 22379460]

[105]
Ashcroft FM. From molecule to malady. Nature  2006; 440(7083): 440-7.
 [http://dx.doi.org/10.1038/nature04707] [PMID: 16554803]

[106]
Waszkielewicz AM, Gunia A, Szkaradek N, Słoczyńska K, Krupińska S, Marona H. Ion channels as drug targets in central nervous system disorders. Curr Med Chem  2013; 20(10): 1241-85.
 [http://dx.doi.org/10.2174/0929867311320100005] [PMID: 23409712]

[107]
Li M, Lester HA. Ion channel diseases of the central nervous system. CNS Drug Rev  2001; 7(2): 214-40.
 [http://dx.doi.org/10.1111/j.1527-3458.2001.tb00196.x] [PMID: 11474425]

[108]
Gielen M, Barilone N, Corringer PJ. The desensitization pathway of GABAA receptors, one subunit at a time. Nat Commun  2020; 11(1): 5369.
 [http://dx.doi.org/10.1038/s41467-020-19218-6] [PMID: 33097732]

[109]
Rhodes KJ, Trimmer JS. Antibody-based validation of CNS ion channel drug targets. J Gen Physiol  2008; 131(5): 407-13.
 [http://dx.doi.org/10.1085/jgp.200709926] [PMID: 18411328]

[110]
Zhang Y, Wang K, Yu Z. Drug development in channelopathies: Allosteric modulation of ligand-gated and voltage-gated ion channels. J Med Chem  2020; 63(24): 15258-78.
 [http://dx.doi.org/10.1021/acs.jmedchem.0c01304] [PMID: 33253554]

[111]
Li S, Wong AH, Liu F. Ligand-gated ion channel interacting proteins and their role in neuroprotection. Front Cell Neurosci  2014; 8: 125.
 [http://dx.doi.org/10.3389/fncel.2014.00125] [PMID: 24847210]

[112]
Sallard E, Letourneur D, Legendre P. Electrophysiology of ionotropic GABA receptors. Cell Mol Life Sci  2021; 78(13): 5341-70.
 [http://dx.doi.org/10.1007/s00018-021-03846-2] [PMID: 34061215]

[113]
Salpietro V, Dixon CL, Guo H, et al. SYNAPS Study Group. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Nat Commun  2019; 10(1): 3094.
 [http://dx.doi.org/10.1038/s41467-019-10910-w] [PMID: 31300657]

[114]
Celli R, Fornai F. Targeting ionotropic glutamate receptors in the treatment of epilepsy. Curr Neuropharmacol  2021; 19(6): 747-65.
 [http://dx.doi.org/10.2174/1570159X18666200831154658] [PMID: 32867642]

[115]
Hanada T. Ionotropic glutamate receptors in epilepsy: A review focusing on AMPA and NMDA receptors. Biomolecules  2020; 10(3): 10.
 [http://dx.doi.org/10.3390/biom10030464] [PMID: 32197322]

[116]
Pinheiro PS, Mulle C. Presynaptic glutamate receptors: Physiological functions and mechanisms of action. Nat Rev Neurosci  2008; 9(6): 423-36.
 [http://dx.doi.org/10.1038/nrn2379] [PMID: 18464791]

[117]
Amin J, Weiss DS. GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital. Nature  1993; 366(6455): 565-9.
 [http://dx.doi.org/10.1038/366565a0] [PMID: 7504783]

[118]
Spurny R, Ramerstorfer J, Price K, et al. Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines. Proc Natl Acad Sci USA  2012; 109(44): E3028-34.
 [http://dx.doi.org/10.1073/pnas.1208208109] [PMID: 23035248]

[119]
Ghit A, Assal D, Al-Shami AS, Hussein DEE. GABAA receptors: Structure, function, pharmacology, and related disorders. J Genet Eng Biotechnol  2021; 19(1): 123.
 [http://dx.doi.org/10.1186/s43141-021-00224-0] [PMID: 34417930]

[120]
Ben-Ari Y. Excitatory actions of gaba during development: The nature of the nurture. Nat Rev Neurosci  2002; 3(9): 728-39.
 [http://dx.doi.org/10.1038/nrn920] [PMID: 12209121]

[121]
Jembrek MJ, Vlainic J. GABA receptors: Pharmacological potential and pitfalls. Curr Pharm Des  2015; 21(34): 4943-59.
 [http://dx.doi.org/10.2174/1381612821666150914121624] [PMID: 26365137]

[122]
Lynch JW. Molecular structure and function of the glycine receptor chloride channel. Physiol Rev  2004; 84(4): 1051-95.
 [http://dx.doi.org/10.1152/physrev.00042.2003] [PMID: 15383648]

[123]
Zhu H, Gouaux E. Architecture and assembly mechanism of native glycine receptors. Nature  2021; 599(7885): 513-7.
 [http://dx.doi.org/10.1038/s41586-021-04022-z] [PMID: 34555840]

[124]
Sheng M, Pak DT. Glutamate receptor anchoring proteins and the molecular organization of excitatory synapses. Ann N Y Acad Sci  1999; 868: 483-93.
 [http://dx.doi.org/10.1111/j.1749-6632.1999.tb11317.x] [PMID: 10414325]

[125]
Traynelis SF, Wollmuth LP, McBain CJ, et al. Glutamate receptor ion channels: Structure, regulation, and function. Pharmacol Rev  2010; 62(3): 405-96.
 [http://dx.doi.org/10.1124/pr.109.002451] [PMID: 20716669]

[126]
Sattler C, Eick T, Hummert S, et al. Unravelling the intricate cooperativity of subunit gating in P2X2 ion channels. Sci Rep  2020; 10(1): 21751.
 [http://dx.doi.org/10.1038/s41598-020-78672-w] [PMID: 33303878]

[127]
Mansoor SE, Lü W, Oosterheert W, Shekhar M, Tajkhorshid E, Gouaux E. X-ray structures define human P2X(3) receptor gating cycle and antagonist action. Nature  2016; 538(7623): 66-71.
 [http://dx.doi.org/10.1038/nature19367] [PMID: 27626375]

[128]
Keramidas A, Lynch JW. An outline of desensitization in pentameric ligand-gated ion channel receptors. Cell Mol Life Sci  2013; 70(7): 1241-53.
 [http://dx.doi.org/10.1007/s00018-012-1133-z] [PMID: 22936353]

[129]
Salter MW, Kalia LV. Src kinases: A hub for NMDA receptor regulation. Nat Rev Neurosci  2004; 5(4): 317-28.
 [http://dx.doi.org/10.1038/nrn1368] [PMID: 15034556]

[130]
Chen BS, Roche KW. Regulation of NMDA receptors by phosphorylation. Neuropharmacology  2007; 53(3): 362-8.
 [http://dx.doi.org/10.1016/j.neuropharm.2007.05.018] [PMID: 17644144]

[131]
Dorszewska J. Cell biology of normal brain aging: Synaptic plasticity-cell death. Aging Clin Exp Res  2013; 25(1): 25-34.
 [http://dx.doi.org/10.1007/s40520-013-0004-2] [PMID: 23740630]

[132]
Shepherd JD, Huganir RL. The cell biology of synaptic plasticity: AMPA receptor trafficking. Annu Rev Cell Dev Biol  2007; 23(1): 613-43.
 [http://dx.doi.org/10.1146/annurev.cellbio.23.090506.123516] [PMID: 17506699]

[133]
Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R. GABA: A pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev  2007; 87(4): 1215-84.
 [http://dx.doi.org/10.1152/physrev.00017.2006] [PMID: 17928584]

[134]
Alexander SP, Peters JA, Kelly E, et al. CGTP Collaborators. The concise guide to pharmacology 2017/18: Ligand-gated ion channels. Br J Pharmacol  2017; 174 (Suppl. 1): S130-59.
 [http://dx.doi.org/10.1111/bph.13879] [PMID: 29055038]

[135]
Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol  2002; 213: 1-47.
 [http://dx.doi.org/10.1016/S0074-7696(02)13011-7] [PMID: 11837891]

[136]
Olsen RW, Sieghart W. GABA A receptors: Subtypes provide diversity of function and pharmacology. Neuropharmacology  2009; 56(1): 141-8.
 [http://dx.doi.org/10.1016/j.neuropharm.2008.07.045] [PMID: 18760291]

[137]
Mody I, De Koninck Y, Otis TS, Soltesz I. Bridging the cleft at GABA synapses in the brain. Trends Neurosci  1994; 17(12): 517-25.
 [http://dx.doi.org/10.1016/0166-2236(94)90155-4] [PMID: 7532336]

[138]
Nusser Z, Cull-Candy S, Farrant M. Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude. Neuron  1997; 19(3): 697-709.
 [http://dx.doi.org/10.1016/S0896-6273(00)80382-7] [PMID: 9331359]

[139]
Succol F, Fiumelli H, Benfenati F, Cancedda L, Barberis A. Intracellular chloride concentration influences the GABAA receptor subunit composition. Nat Commun  2012; 3(1): 738.
 [http://dx.doi.org/10.1038/ncomms1744] [PMID: 22415829]

[140]
Farrant M, Nusser Z. Variations on an inhibitory theme: Phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci  2005; 6(3): 215-29.
 [http://dx.doi.org/10.1038/nrn1625] [PMID: 15738957]

[141]
Bryson A, Hatch RJ, Zandt BJ, et al. GABA-mediated tonic inhibition differentially modulates gain in functional subtypes of cortical interneurons. Proc Natl Acad Sci USA  2020; 117(6): 3192-202.
 [http://dx.doi.org/10.1073/pnas.1906369117] [PMID: 31974304]

[142]
Glykys J, Mody I. Activation of GABAA receptors: Views from outside the synaptic cleft. Neuron  2007; 56(5): 763-70.
 [http://dx.doi.org/10.1016/j.neuron.2007.11.002] [PMID: 18054854]

[143]
Belelli D, Harrison NL, Maguire J, Macdonald RL, Walker MC, Cope DW. Extrasynaptic GABAA receptors: Form, pharmacology, and function. J Neurosci  2009; 29(41): 12757-63.
 [http://dx.doi.org/10.1523/JNEUROSCI.3340-09.2009] [PMID: 19828786]

[144]
Reiner A, Levitz J. Glutamatergic signaling in the central nervous system: Ionotropic and metabotropic receptors in concert. Neuron  2018; 98(6): 1080-98.
 [http://dx.doi.org/10.1016/j.neuron.2018.05.018] [PMID: 29953871]

[145]
López-Corcuera B, Geerlings A, Aragón C. Glycine neurotransmitter transporters: An update. Mol Membr Biol  2001; 18(1): 13-20.
 [http://dx.doi.org/10.1080/09687680010028762] [PMID: 11396606]

[146]
Betz H, Langosch D, Hoch W, et al. Structure and expression of inhibitory glycine receptors. Adv Exp Med Biol  1991; 287: 421-9.
 [http://dx.doi.org/10.1007/978-1-4684-5907-4_37] [PMID: 1722070]

[147]
Dutertre S, Becker CM, Betz H. Inhibitory glycine receptors: An update. J Biol Chem  2012; 287(48): 40216-23.
 [http://dx.doi.org/10.1074/jbc.R112.408229] [PMID: 23038260]

[148]
Burgos CF, Yévenes GE, Aguayo LG. Structure and pharmacologic modulation of inhibitory glycine receptors. Mol Pharmacol  2016; 90(3): 318-25.
 [http://dx.doi.org/10.1124/mol.116.105726] [PMID: 27401877]

[149]
Avila A, Nguyen L, Rigo JM. Glycine receptors and brain development. Front Cell Neurosci  2013; 7: 184.
 [http://dx.doi.org/10.3389/fncel.2013.00184] [PMID: 24155690]

[150]
Zeilhofer HU, Wildner H, Yévenes GE. Fast synaptic inhibition in spinal sensory processing and pain control. Physiol Rev  2012; 92(1): 193-235.
 [http://dx.doi.org/10.1152/physrev.00043.2010] [PMID: 22298656]

[151]
Alvarez FJ, Benito-Gonzalez A, Siembab VC. Principles of interneuron development learned from Renshaw cells and the motoneuron recurrent inhibitory circuit. Ann N Y Acad Sci  2013; 1279(1): 22-31.
 [http://dx.doi.org/10.1111/nyas.12084] [PMID: 23530999]

[152]
Zeilhofer HU, Werynska K, Gingras J, Yévenes GE. Glycine receptors in spinal nociceptive control-an update. Biomolecules  2021; 11(6): 11.
 [http://dx.doi.org/10.3390/biom11060846] [PMID: 34204137]

[153]
Apostolides PF, Trussell LO. Rapid, activity-independent turnover of vesicular transmitter content at a mixed glycine/GABA synapse. J Neurosci  2013; 33(11): 4768-81.
 [http://dx.doi.org/10.1523/JNEUROSCI.5555-12.2013] [PMID: 23486948]

[154]
Edwards RH. The neurotransmitter cycle and quantal size. Neuron  2007; 55(6): 835-58.
 [http://dx.doi.org/10.1016/j.neuron.2007.09.001] [PMID: 17880890]

[155]
Harvey RJ, Topf M, Harvey K, Rees MI. The genetics of hyperekplexia: More than startle! Trends Genet  2008; 24(9): 439-47.
 [http://dx.doi.org/10.1016/j.tig.2008.06.005] [PMID: 18707791]

[156]
Lynch JW, Callister RJ. Glycine receptors: A new therapeutic target in pain pathways. Curr Opin Investig Drugs  2006; 7(1): 48-53.
 [PMID: 16425671]

[157]
Grothe B. New roles for synaptic inhibition in sound localization. Nat Rev Neurosci  2003; 4(7): 540-50.
 [http://dx.doi.org/10.1038/nrn1136] [PMID: 12838329]

[158]
Soto D, Altafaj X, Sindreu C, Bayés A. Glutamate receptor mutations in psychiatric and neurodevelopmental disorders. Commun Integr Biol  2014; 7(1): e27887.
 [http://dx.doi.org/10.4161/cib.27887] [PMID: 24605182]

[159]
Trippe J, Steinke K, Orth A, Faustmann PM, Hollmann M, Haase CG. Autoantibodies to glutamate receptor antigens in multiple sclerosis and Rasmussen’s encephalitis. Neuroimmunomodulation  2014; 21(4): 189-94.
 [http://dx.doi.org/10.1159/000356519] [PMID: 24504116]

[160]
Salling MC, Harrison NL. Strychnine-sensitive glycine receptors on pyramidal neurons in layers II/III of the mouse prefrontal cortex are tonically activated. J Neurophysiol  2014; 112(5): 1169-78.
 [http://dx.doi.org/10.1152/jn.00714.2013] [PMID: 24872538]

[161]
Van den Eynden J, Ali SS, Horwood N, et al. Glycine and glycine receptor signalling in non-neuronal cells. Front Mol Neurosci  2009; 2: 9.
 [http://dx.doi.org/10.3389/neuro.02.009.2009] [PMID: 19738917]

[162]
Lewis RS. Calcium signaling mechanisms in T lymphocytes. Annu Rev Immunol  2001; 19(1): 497-521.
 [http://dx.doi.org/10.1146/annurev.immunol.19.1.497] [PMID: 11244045]

[163]
Passaro AP, Lebos AL, Yao Y, Stice SL. Immune response in neurological pathology: Emerging role of central and peripheral immune crosstalk. Front Immunol  2021; 12: 676621.
 [http://dx.doi.org/10.3389/fimmu.2021.676621] [PMID: 34177918]

[164]
Webb TI, Lynch JW. Molecular pharmacology of the glycine receptor chloride channel. Curr Pharm Des  2007; 13(23): 2350-67.
 [http://dx.doi.org/10.2174/138161207781368693] [PMID: 17692006]

[165]
Schaefer N, Roemer V, Janzen D, Villmann C. Impaired glycine receptor trafficking in neurological diseases. Front Mol Neurosci  2018; 11: 291.
 [http://dx.doi.org/10.3389/fnmol.2018.00291] [PMID: 30186111]

[166]
Dineley KT, Pandya AA, Yakel JL. Nicotinic ACh receptors as therapeutic targets in CNS disorders. Trends Pharmacol Sci  2015; 36(2): 96-108.
 [http://dx.doi.org/10.1016/j.tips.2014.12.002] [PMID: 25639674]

[167]
Zoli M, Pistillo F, Gotti C. Diversity of native nicotinic receptor subtypes in mammalian brain. Neuropharmacology  2015; 96(Pt B): 302-11.
 [http://dx.doi.org/10.1016/j.neuropharm.2014.11.003] [PMID: 25460185]

[168]
Kalkman HO, Feuerbach D. Modulatory effects of α7 nAChRs on the immune system and its relevance for CNS disorders. Cell Mol Life Sci  2016; 73(13): 2511-30.
 [http://dx.doi.org/10.1007/s00018-016-2175-4] [PMID: 26979166]

[169]
Noda M, Kobayashi AI. Nicotine inhibits activation of microglial proton currents via interactions with α7 acetylcholine receptors. J Physiol Sci  2017; 67(1): 235-45.
 [http://dx.doi.org/10.1007/s12576-016-0460-5] [PMID: 27256075]

[170]
Young JW, Geyer MA. Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia. Biochem Pharmacol  2013; 86(8): 1122-32.
 [http://dx.doi.org/10.1016/j.bcp.2013.06.031] [PMID: 23856289]

[171]
Zoli M, Pucci S, Vilella A, Gotti C. Neuronal and extraneuronal nicotinic acetylcholine receptors. Curr Neuropharmacol  2018; 16(4): 338-49.
 [http://dx.doi.org/10.2174/1570159X15666170912110450] [PMID: 28901280]

[172]
Fujii T, Mashimo M, Moriwaki Y, et al. Expression and function of the cholinergic system in immune cells. Front Immunol  2017; 8: 1085.
 [http://dx.doi.org/10.3389/fimmu.2017.01085] [PMID: 28932225]

[173]
Rosas-Ballina M, Olofsson PS, Ochani M, et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science  2011; 334(6052): 98-101.
 [http://dx.doi.org/10.1126/science.1209985] [PMID: 21921156]

[174]
Wang H, Yu M, Ochani M, et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature  2003; 421(6921): 384-8.
 [http://dx.doi.org/10.1038/nature01339] [PMID: 12508119]

[175]
Kawashima K, Fujii T, Moriwaki Y, Misawa H, Horiguchi K. Reconciling neuronally and nonneuronally derived acetylcholine in the regulation of immune function. Ann N Y Acad Sci  2012; 1261(1): 7-17.
 [http://dx.doi.org/10.1111/j.1749-6632.2012.06516.x] [PMID: 22823388]

[176]
Paradiso KG, Steinbach JH. Nicotine is highly effective at producing desensitization of rat alpha4beta2 neuronal nicotinic receptors. J Physiol  2003; 553(Pt 3): 857-71.
 [http://dx.doi.org/10.1113/jphysiol.2003.053447] [PMID: 14555718]

[177]
Picciotto MR, Addy NA, Mineur YS, Brunzell DH. It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Prog Neurobiol  2008; 84(4): 329-42.
 [http://dx.doi.org/10.1016/j.pneurobio.2007.12.005] [PMID: 18242816]

[178]
Conejero-Goldberg C, Davies P, Ulloa L. Alpha7 nicotinic acetylcholine receptor: A link between inflammation and neurodegeneration. Neurosci Biobehav Rev  2008; 32(4): 693-706.
 [http://dx.doi.org/10.1016/j.neubiorev.2007.10.007] [PMID: 18180036]

[179]
de Jonge WJ, Ulloa L. The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol  2007; 151(7): 915-29.
 [http://dx.doi.org/10.1038/sj.bjp.0707264] [PMID: 17502850]

[180]
Corradi J, Bouzat C. Understanding the bases of function and modulation of α7 nicotinic receptors: Implications for drug discovery. Mol Pharmacol  2016; 90(3): 288-99.
 [http://dx.doi.org/10.1124/mol.116.104240] [PMID: 27190210]

[181]
Ahmad S, She Z, Kraatz HB. Electrochemical studies of human nAChR a7 subunit phosphorylation by kinases PKA, PKC and Src. Anal Biochem  2019; 574: 46-56.
 [http://dx.doi.org/10.1016/j.ab.2019.03.012] [PMID: 30914244]

[182]
Quik M, Bordia T, O’Leary K. Nicotinic receptors as CNS targets for Parkinson’s disease. Biochem Pharmacol  2007; 74(8): 1224-34.
 [http://dx.doi.org/10.1016/j.bcp.2007.06.015] [PMID: 17631864]

[183]
Ghasemi M, Hadipour-Niktarash A. Pathologic role of neuronal nicotinic acetylcholine receptors in epileptic disorders: Implication for pharmacological interventions. Rev Neurosci  2015; 26(2): 199-223.
 [http://dx.doi.org/10.1515/revneuro-2014-0044] [PMID: 25565544]

[184]
Decker MW, Meyer MD, Sullivan JP. The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control. Expert Opin Investig Drugs  2001; 10(10): 1819-30.
 [http://dx.doi.org/10.1517/13543784.10.10.1819] [PMID: 11772288]

[185]
Quik M, Wonnacott S. α6β2* and α4β2* nicotinic acetylcholine receptors as drug targets for Parkinson’s disease. Pharmacol Rev  2011; 63(4): 938-66.
 [http://dx.doi.org/10.1124/pr.110.003269] [PMID: 21969327]

[186]
Michely J, Eldar E, Martin IM, Dolan RJ. A mechanistic account of serotonin’s impact on mood. Nat Commun  2020; 11(1): 2335.
 [http://dx.doi.org/10.1038/s41467-020-16090-2] [PMID: 32393738]

[187]
Baganz NL, Blakely RD. A dialogue between the immune system and brain, spoken in the language of serotonin. ACS Chem Neurosci  2013; 4(1): 48-63.
 [http://dx.doi.org/10.1021/cn300186b] [PMID: 23336044]

[188]
Hoyer D, Hannon JP, Martin GR. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav  2002; 71(4): 533-54.
 [http://dx.doi.org/10.1016/S0091-3057(01)00746-8] [PMID: 11888546]

[189]
Nayak SV, Rondé P, Spier AD, Lummis SC, Nichols RA. Nicotinic receptors co-localize with 5-HT(3) serotonin receptors on striatal nerve terminals. Neuropharmacology  2000; 39(13): 2681-90.
 [http://dx.doi.org/10.1016/S0028-3908(00)00109-X] [PMID: 11044738]

[190]
Lummis SC. 5-HT(3) receptors. J Biol Chem  2012; 287(48): 40239-45.
 [http://dx.doi.org/10.1074/jbc.R112.406496] [PMID: 23038271]

[191]
Derkach V, Surprenant A, North RA. 5-HT3 receptors are membrane ion channels. Nature  1989; 339(6227): 706-9.
 [http://dx.doi.org/10.1038/339706a0] [PMID: 2472553]

[192]
Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science  1991; 254(5030): 432-7.
 [http://dx.doi.org/10.1126/science.1718042] [PMID: 1718042]

[193]
Yang J. Ion permeation through 5-hydroxytryptamine-gated channels in neuroblastoma N18 cells. J Gen Physiol  1990; 96(6): 1177-98.
 [http://dx.doi.org/10.1085/jgp.96.6.1177] [PMID: 2286832]

[194]
Teixeira CM, Rosen ZB, Suri D, et al. Hippocampal 5-HT input regulates memory formation and schaffer collateral excitation. Neuron  2018; 98(5): 992-1004.e4.
 [http://dx.doi.org/10.1016/j.neuron.2018.04.030] [PMID: 29754752]

[195]
Kilpatrick GJ, Jones BJ, Tyers MB. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature  1987; 330(6150): 746-8.
 [http://dx.doi.org/10.1038/330746a0] [PMID: 3696238]

[196]
Zhong W, Shahbaz O, Teskey G, et al. Mechanisms of nausea and vomiting: Current knowledge and recent advances in intracellular emetic signaling systems. Int J Mol Sci  2021; 22(11): 22.
 [http://dx.doi.org/10.3390/ijms22115797] [PMID: 34071460]

[197]
Tecott LH, Maricq AV, Julius D. Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proc Natl Acad Sci USA  1993; 90(4): 1430-4.
 [http://dx.doi.org/10.1073/pnas.90.4.1430] [PMID: 8434003]

[198]
Faerber L, Drechsler S, Ladenburger S, Gschaidmeier H, Fischer W. The neuronal 5-HT3 receptor network after 20 years of research--evolving concepts in management of pain and inflammation. Eur J Pharmacol  2007; 560(1): 1-8.
 [http://dx.doi.org/10.1016/j.ejphar.2007.01.028] [PMID: 17316606]

[199]
Kishi T, Mukai T, Matsuda Y, Iwata N. Selective serotonin 3 receptor antagonist treatment for schizophrenia: Meta-analysis and systematic review. Neuromolecular Med  2014; 16(1): 61-9.
 [http://dx.doi.org/10.1007/s12017-013-8251-0] [PMID: 23896722]

[200]
Fakhfouri G, Rahimian R, Dyhrfjeld-Johnsen J, Zirak MR, Beaulieu JM. 5-HT3 receptor antagonists in neurologic and neuropsychiatric disorders: The iceberg still lies beneath the surface. Pharmacol Rev  2019; 71(3): 383-412.
 [http://dx.doi.org/10.1124/pr.118.015487] [PMID: 31243157]

[201]
Theriot J, Wermuth HR, Ashurst JV. Antiemetic serotonin-5-HT3 receptor blockers. Treasure Island, (FL): StatPearls 2021.

[202]
Terashima A, Cotton L, Dev KK, et al. Regulation of synaptic strength and AMPA receptor subunit composition by PICK1. J Neurosci  2004; 24(23): 5381-90.
 [http://dx.doi.org/10.1523/JNEUROSCI.4378-03.2004] [PMID: 15190111]

[203]
Schousboe A. Transport and metabolism of glutamate and GABA in neurons are glial cells. Int Rev Neurobiol  1981; 22: 1-45.
 [http://dx.doi.org/10.1016/S0074-7742(08)60289-5] [PMID: 6115823]

[204]
Huang YH, Bergles DE. Glutamate transporters bring competition to the synapse. Curr Opin Neurobiol  2004; 14(3): 346-52.
 [http://dx.doi.org/10.1016/j.conb.2004.05.007] [PMID: 15194115]

[205]
Rothstein JD, Martin L, Levey AI, et al. Localization of neuronal and glial glutamate transporters. Neuron  1994; 13(3): 713-25.
 [http://dx.doi.org/10.1016/0896-6273(94)90038-8] [PMID: 7917301]

[206]
Lodge D. The history of the pharmacology and cloning of ionotropic glutamate receptors and the development of idiosyncratic nomenclature. Neuropharmacology  2009; 56(1): 6-21.
 [http://dx.doi.org/10.1016/j.neuropharm.2008.08.006] [PMID: 18765242]

[207]
Lubin FD, Roth TL, Sweatt JD. Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci  2008; 28(42): 10576-86.
 [http://dx.doi.org/10.1523/JNEUROSCI.1786-08.2008] [PMID: 18923034]

[208]
Cohen S, Greenberg ME. Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Annu Rev Cell Dev Biol  2008; 24(1): 183-209.
 [http://dx.doi.org/10.1146/annurev.cellbio.24.110707.175235] [PMID: 18616423]

[209]
Keinänen K, Wisden W, Sommer B, et al. A family of AMPA-selective glutamate receptors. Science  1990; 249(4968): 556-60.
 [http://dx.doi.org/10.1126/science.2166337] [PMID: 2166337]

[210]
Mosbacher J, Schoepfer R, Monyer H, Burnashev N, Seeburg PH, Ruppersberg JP. A molecular determinant for submillisecond desensitization in glutamate receptors. Science  1994; 266(5187): 1059-62.
 [http://dx.doi.org/10.1126/science.7973663] [PMID: 7973663]

[211]
Kessels HW, Malinow R. Synaptic AMPA receptor plasticity and behavior. Neuron  2009; 61(3): 340-50.
 [http://dx.doi.org/10.1016/j.neuron.2009.01.015] [PMID: 19217372]

[212]
Diering GH, Huganir RL. The AMPA receptor code of synaptic plasticity. Neuron  2018; 100(2): 314-29.
 [http://dx.doi.org/10.1016/j.neuron.2018.10.018] [PMID: 30359599]

[213]
Alt A, Nisenbaum ES, Bleakman D, Witkin JM. A role for AMPA receptors in mood disorders. Biochem Pharmacol  2006; 71(9): 1273-88.
 [http://dx.doi.org/10.1016/j.bcp.2005.12.022] [PMID: 16442080]

[214]
Francis PT. Glutamatergic systems in Alzheimer’s disease. Int J Geriatr Psychiatry  2003; 18 (Suppl. 1): S15-21.
 [http://dx.doi.org/10.1002/gps.934] [PMID: 12973746]

[215]
Henley JM, Wilkinson KA. Synaptic AMPA receptor composition in development, plasticity and disease. Nat Rev Neurosci  2016; 17(6): 337-50.
 [http://dx.doi.org/10.1038/nrn.2016.37] [PMID: 27080385]

[216]
Benke TA, Lüthi A, Isaac JT, Collingridge GL. Modulation of AMPA receptor unitary conductance by synaptic activity. Nature  1998; 393(6687): 793-7.
 [http://dx.doi.org/10.1038/31709] [PMID: 9655394]

[217]
Plant K, Pelkey KA, Bortolotto ZA, et al. Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci  2006; 9(5): 602-4.
 [http://dx.doi.org/10.1038/nn1678] [PMID: 16582904]

[218]
Sobolevsky AI, Rosconi MP, Gouaux E. X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor. Nature  2009; 462(7274): 745-56.
 [http://dx.doi.org/10.1038/nature08624] [PMID: 19946266]

[219]
Lu W, Shi Y, Jackson AC, et al. Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Neuron  2009; 62(2): 254-68.
 [http://dx.doi.org/10.1016/j.neuron.2009.02.027] [PMID: 19409270]

[220]
Renner MC, Albers EH, Gutierrez-Castellanos N, et al. Synaptic plasticity through activation of GluA3-containing AMPA-receptors. eLife  2017; 6: 6.
 [http://dx.doi.org/10.7554/eLife.25462] [PMID: 28762944]

[221]
Liu SJ, Zukin RS. Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death. Trends Neurosci  2007; 30(3): 126-34.
 [http://dx.doi.org/10.1016/j.tins.2007.01.006] [PMID: 17275103]

[222]
Braithwaite SP, Xia H, Malenka RC. Differential roles for NSF and GRIP/ABP in AMPA receptor cycling. Proc Natl Acad Sci USA  2002; 99(10): 7096-101.
 [http://dx.doi.org/10.1073/pnas.102156099] [PMID: 12011465]

[223]
Dev KK, Nishimune A, Henley JM, Nakanishi S. The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology  1999; 38(5): 635-44.
 [http://dx.doi.org/10.1016/S0028-3908(98)00230-5] [PMID: 10340301]

[224]
Dong H, O’Brien RJ, Fung ET, Lanahan AA, Worley PF, Huganir RL. GRIP: A synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature  1997; 386(6622): 279-84.
 [http://dx.doi.org/10.1038/386279a0] [PMID: 9069286]

[225]
Goldberg JH, Tamas G, Aronov D, Yuste R. Calcium microdomains in aspiny dendrites. Neuron  2003; 40(4): 807-21.
 [http://dx.doi.org/10.1016/S0896-6273(03)00714-1] [PMID: 14622584]

[226]
O’Neill MJ, Bleakman D, Zimmerman DM, Nisenbaum ES. AMPA receptor potentiators for the treatment of CNS disorders. Curr Drug Targets CNS Neurol Disord  2004; 3(3): 181-94.
 [http://dx.doi.org/10.2174/1568007043337508] [PMID: 15180479]

[227]
Watkins JC. The synthesis of some acidic amino acids possessing neuropharmacological activity. J Med Pharm Chem  1962; 91(6): 1187-99.
 [http://dx.doi.org/10.1021/jm01241a010] [PMID: 14056452]

[228]
Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity: Impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci  2013; 14(6): 383-400.
 [http://dx.doi.org/10.1038/nrn3504] [PMID: 23686171]

[229]
Kleckner NW, Dingledine R. Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science  1988; 241(4867): 835-7.
 [http://dx.doi.org/10.1126/science.2841759] [PMID: 2841759]

[230]
Schmid SM, Hollmann M. To gate or not to gate: Are the delta subunits in the glutamate receptor family functional ion channels? Mol Neurobiol  2008; 37(2-3): 126-41.
 [http://dx.doi.org/10.1007/s12035-008-8025-0] [PMID: 18521762]

[231]
Ulbrich MH, Isacoff EY. Subunit counting in membrane-bound proteins. Nat Methods  2007; 4(4): 319-21.
 [http://dx.doi.org/10.1038/nmeth1024] [PMID: 17369835]

[232]
Ulbrich MH, Isacoff EY. Rules of engagement for NMDA receptor subunits. Proc Natl Acad Sci USA  2008; 105(37): 14163-8.
 [http://dx.doi.org/10.1073/pnas.0802075105] [PMID: 18779583]

[233]
Yao Y, Harrison CB, Freddolino PL, Schulten K, Mayer ML. Molecular mechanism of ligand recognition by NR3 subtype glutamate receptors. EMBO J  2008; 27(15): 2158-70.
 [http://dx.doi.org/10.1038/emboj.2008.140] [PMID: 18636091]

[234]
Furukawa H, Singh SK, Mancusso R, Gouaux E. Subunit arrangement and function in NMDA receptors. Nature  2005; 438(7065): 185-92.
 [http://dx.doi.org/10.1038/nature04089] [PMID: 16281028]

[235]
Mayer ML, Westbrook GL, Guthrie PB. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature  1984; 309(5965): 261-3.
 [http://dx.doi.org/10.1038/309261a0] [PMID: 6325946]

[236]
Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature  1984; 307(5950): 462-5.
 [http://dx.doi.org/10.1038/307462a0] [PMID: 6320006]

[237]
Ault B, Evans RH, Francis AA, Oakes DJ, Watkins JC. Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations. J Physiol  1980; 307(1): 413-28.
 [http://dx.doi.org/10.1113/jphysiol.1980.sp013443] [PMID: 6259339]

[238]
Cotman CW, Monaghan DT, Ganong AH. Excitatory amino acid neurotransmission: NMDA receptors and Hebb-type synaptic plasticity. Annu Rev Neurosci  1988; 11(1): 61-80.
 [http://dx.doi.org/10.1146/annurev.ne.11.030188.000425] [PMID: 2452598]

[239]
Collingridge GL, Singer W. Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol Sci  1990; 11(7): 290-6.
 [http://dx.doi.org/10.1016/0165-6147(90)90011-V] [PMID: 2167544]

[240]
Yu SP, Yeh C, Strasser U, Tian M, Choi DW. NMDA receptor-mediated K+ efflux and neuronal apoptosis. Science  1999; 284(5412): 336-9.
 [http://dx.doi.org/10.1126/science.284.5412.336] [PMID: 10195902]

[241]
Yu XM, Salter MW. Src, a molecular switch governing gain control of synaptic transmission mediated by N-methyl-D-aspartate receptors. Proc Natl Acad Sci USA  1999; 96(14): 7697-704.
 [http://dx.doi.org/10.1073/pnas.96.14.7697] [PMID: 10393883]

[242]
Regalado MP, Villarroel A, Lerma J. Intersubunit cooperativity in the NMDA receptor. Neuron  2001; 32(6): 1085-96.
 [http://dx.doi.org/10.1016/S0896-6273(01)00539-6] [PMID: 11754839]

[243]
Vissel B, Krupp JJ, Heinemann SF, Westbrook GL. A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux. Nat Neurosci  2001; 4(6): 587-96.
 [http://dx.doi.org/10.1038/88404] [PMID: 11369939]

[244]
Erreger K, Traynelis SF. Allosteric interaction between zinc and glutamate binding domains on NR2A causes desensitization of NMDA receptors. J Physiol  2005; 569(Pt 2): 381-93.
 [http://dx.doi.org/10.1113/jphysiol.2005.095497] [PMID: 16166158]

[245]
Sessoms-Sikes S, Honse Y, Lovinger DM, Colbran RJ. CaMKIIalpha enhances the desensitization of NR2B-containing NMDA receptors by an autophosphorylation-dependent mechanism. Mol Cell Neurosci  2005; 29(1): 139-47.
 [http://dx.doi.org/10.1016/j.mcn.2005.01.006] [PMID: 15866054]

[246]
Hu B, Zheng F. Differential effects on current kinetics by point mutations in the lurcher motif of NR1/NR2A receptors. J Pharmacol Exp Ther  2005; 312(3): 899-904.
 [http://dx.doi.org/10.1124/jpet.104.077388] [PMID: 15501991]

[247]
Mota SI, Ferreira IL, Rego AC. Dysfunctional synapse in Alzheimer's disease - a focus on NMDA receptors. Neuropharmacology  2014; 76(Pt A): 16-26.

[248]
Verhagen Metman L, Morris MJ, Farmer C, et al. Huntington’s disease: A randomized, controlled trial using the NMDA-antagonist amantadine. Neurology  2002; 59(5): 694-9.
 [http://dx.doi.org/10.1212/WNL.59.5.694] [PMID: 12221159]

[249]
Zhou Q, Sheng M. NMDA receptors in nervous system diseases. Neuropharmacology  2013; 74: 69-75.
 [http://dx.doi.org/10.1016/j.neuropharm.2013.03.030] [PMID: 23583930]

[250]
Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sánchez E, Gutiérrez-Rojas L, Meana JJ. Antidepressant efficacy and tolerability of ketamine and esketamine: A critical review. CNS Drugs  2018; 32(5): 411-20.
 [http://dx.doi.org/10.1007/s40263-018-0519-3] [PMID: 29736744]

[251]
Zhou D, Xie C, Li X, et al. Rare presence of autoantibodies targeting to NMDA and GABAA receptors in schizophrenia patients. Schizophr Res  2021; S0920-9964(21)00486-2.
 [http://dx.doi.org/10.1016/j.schres.2021.12.002] [PMID: 34916095]

[252]
Bigal ME, Bordini CA, Tepper SJ, Speciali JG. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia  2002; 22(5): 345-53.
 [http://dx.doi.org/10.1046/j.1468-2982.2002.00364.x] [PMID: 12110110]

[253]
Foster AC, Mena EE, Monaghan DT, Cotman CW. Synaptic localization of kainic acid binding sites. Nature  1981; 289(5793): 73-5.
 [http://dx.doi.org/10.1038/289073a0] [PMID: 6256647]

[254]
Selvakumar P, Lee J, Khanra N, et al. Structural and compositional diversity in the kainate receptor family. Cell Rep  2021; 37(4): 109891.
 [http://dx.doi.org/10.1016/j.celrep.2021.109891] [PMID: 34706237]

[255]
Contractor A, Mulle C, Swanson GT. Kainate receptors coming of age: Milestones of two decades of research. Trends Neurosci  2011; 34(3): 154-63.
 [http://dx.doi.org/10.1016/j.tins.2010.12.002] [PMID: 21256604]

[256]
Valbuena S, Lerma J. Kainate receptors, homeostatic gatekeepers of synaptic plasticity. Neuroscience  2021; 456: 17-26.
 [http://dx.doi.org/10.1016/j.neuroscience.2019.11.050] [PMID: 31866560]

[257]
Veran J, Kumar J, Pinheiro PS, et al. Zinc potentiates GluK3 glutamate receptor function by stabilizing the ligand binding domain dimer interface. Neuron  2012; 76(3): 565-78.
 [http://dx.doi.org/10.1016/j.neuron.2012.08.027] [PMID: 23141068]

[258]
Pollok S, Reiner A. Subunit-selective iGluR antagonists can potentiate heteromeric receptor responses by blocking desensitization. Proc Natl Acad Sci USA  2020; 117(41): 25851-8.
 [http://dx.doi.org/10.1073/pnas.2007471117] [PMID: 32999066]

[259]
Cui C, Mayer ML. Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7. J Neurosci  1999; 19(19): 8281-91.
 [http://dx.doi.org/10.1523/JNEUROSCI.19-19-08281.1999] [PMID: 10493729]

[260]
Gallyas F Jr, Ball SM, Molnar E. Assembly and cell surface expression of KA-2 subunit-containing kainate receptors. J Neurochem  2003; 86(6): 1414-27.
 [http://dx.doi.org/10.1046/j.1471-4159.2003.01945.x] [PMID: 12950450]

[261]
Herb A, Burnashev N, Werner P, Sakmann B, Wisden W, Seeburg PH. The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron  1992; 8(4): 775-85.
 [http://dx.doi.org/10.1016/0896-6273(92)90098-X] [PMID: 1373632]

[262]
Werner P, Voigt M, Keinänen K, Wisden W, Seeburg PH. Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature  1991; 351(6329): 742-4.
 [http://dx.doi.org/10.1038/351742a0] [PMID: 1648176]

[263]
Jane DE, Lodge D, Collingridge GL. Kainate receptors: Pharmacology, function and therapeutic potential. Neuropharmacology  2009; 56(1): 90-113.
 [http://dx.doi.org/10.1016/j.neuropharm.2008.08.023] [PMID: 18793656]

[264]
Paternain AV, Herrera MT, Nieto MA, Lerma J. GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors. J Neurosci  2000; 20(1): 196-205.
 [http://dx.doi.org/10.1523/JNEUROSCI.20-01-00196.2000] [PMID: 10627597]

[265]
Vesikansa A, Sallert M, Taira T, Lauri SE. Activation of kainate receptors controls the number of functional glutamatergic synapses in the area CA1 of rat hippocampus. J Physiol  2007; 583(Pt 1): 145-57.
 [http://dx.doi.org/10.1113/jphysiol.2007.133975] [PMID: 17569736]

[266]
Pinheiro PS, Perrais D, Coussen F, et al. GluR7 is an essential subunit of presynaptic kainate autoreceptors at hippocampal mossy fiber synapses. Proc Natl Acad Sci USA  2007; 104(29): 12181-6.
 [http://dx.doi.org/10.1073/pnas.0608891104] [PMID: 17620617]

[267]
Arora V, Pecoraro V, Aller MI, Román C, Paternain AV, Lerma J. Increased grik4 gene dosage causes imbalanced circuit output and human disease-related behaviors. Cell Rep  2018; 23(13): 3827-38.
 [http://dx.doi.org/10.1016/j.celrep.2018.05.086] [PMID: 29949767]

[268]
Wong AY, MacLean DM, Bowie D. Na+/Cl- dipole couples agonist binding to kainate receptor activation. J Neurosci  2007; 27(25): 6800-9.
 [http://dx.doi.org/10.1523/JNEUROSCI.0284-07.2007] [PMID: 17581967]

[269]
Vignes M, Collingridge GL. The synaptic activation of kainate receptors. Nature  1997; 388(6638): 179-82.
 [http://dx.doi.org/10.1038/40639] [PMID: 9217158]

[270]
Rivera R, Rozas JL, Lerma J. PKC-dependent autoregulation of membrane kainate receptors. EMBO J  2007; 26(20): 4359-67.
 [http://dx.doi.org/10.1038/sj.emboj.7601865] [PMID: 17898803]

[271]
Rozas JL. Metabotropic actions of kainate receptors in dorsal root ganglion cells. Adv Exp Med Biol  2011; 717: 69-80.
 [http://dx.doi.org/10.1007/978-1-4419-9557-5_7] [PMID: 21713668]

[272]
Rozas JL, Paternain AV, Lerma J. Noncanonical signaling by ionotropic kainate receptors. Neuron  2003; 39(3): 543-53.
 [http://dx.doi.org/10.1016/S0896-6273(03)00436-7] [PMID: 12895426]

[273]
Nadler JV. Minireview. Kainic acid as a tool for the study of temporal lobe epilepsy. Life Sci  1981; 29(20): 2031-42.
 [http://dx.doi.org/10.1016/0024-3205(81)90659-7] [PMID: 7031398]

[274]
Sommer B, Burnashev N, Verdoorn TA, Keinänen K, Sakmann B, Seeburg PH. A glutamate receptor channel with high affinity for domoate and kainate. EMBO J  1992; 11(4): 1651-6.
 [http://dx.doi.org/10.1002/j.1460-2075.1992.tb05211.x] [PMID: 1373382]

[275]
Ko S, Zhao MG, Toyoda H, Qiu CS, Zhuo M. Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)- or GluR6-deficient mice. J Neurosci  2005; 25(4): 977-84.
 [http://dx.doi.org/10.1523/JNEUROSCI.4059-04.2005] [PMID: 15673679]

[276]
McCarran WJ, Goldberg MP. White matter axon vulnerability to AMPA/kainate receptor-mediated ischemic injury is developmentally regulated. J Neurosci  2007; 27(15): 4220-9.
 [http://dx.doi.org/10.1523/JNEUROSCI.5542-06.2007] [PMID: 17429000]

[277]
Xu J, Liu Y, Zhang GY. Neuroprotection of GluR5-containing kainate receptor activation against ischemic brain injury through decreasing tyrosine phosphorylation of N-methyl-D-aspartate receptors mediated by Src kinase. J Biol Chem  2008; 283(43): 29355-66.
 [http://dx.doi.org/10.1074/jbc.M800393200] [PMID: 18678878]

[278]
Braga MF, Aroniadou-Anderjaska V, Li H. The physiological role of kainate receptors in the amygdala. Mol Neurobiol  2004; 30(2): 127-41.
 [http://dx.doi.org/10.1385/MN:30:2:127] [PMID: 15475623]

[279]
Li H, Chen A, Xing G, Wei ML, Rogawski MA. Kainate receptor-mediated heterosynaptic facilitation in the amygdala. Nat Neurosci  2001; 4(6): 612-20.
 [http://dx.doi.org/10.1038/88432] [PMID: 11369942]

[280]
Aller MI, Pecoraro V, Paternain AV, Canals S, Lerma J. Increased dosage of high-affinity kainate receptor gene grik4 alters synaptic transmission and reproduces autism spectrum disorders features. J Neurosci  2015; 35(40): 13619-28.
 [http://dx.doi.org/10.1523/JNEUROSCI.2217-15.2015] [PMID: 26446216]

[281]
Benes FM, Vincent SL, Todtenkopf M. The density of pyramidal and nonpyramidal neurons in anterior cingulate cortex of schizophrenic and bipolar subjects. Biol Psychiatry  2001; 50(6): 395-406.
 [http://dx.doi.org/10.1016/S0006-3223(01)01084-8] [PMID: 11566156]

[282]
Meador-Woodruff JH, Davis KL, Haroutunian V. Abnormal kainate receptor expression in prefrontal cortex in schizophrenia. Neuropsychopharmacology  2001; 24(5): 545-52.
 [http://dx.doi.org/10.1016/S0893-133X(00)00189-5] [PMID: 11282254]

[283]
Kranzler HR, Armeli S, Feinn R, Tennen H, Gelernter J, Covault J. GRIK1 genotype moderates topiramate’s effects on daily drinking level, expectations of alcohol’s positive effects and desire to drink. Int J Neuropsychopharmacol  2014; 17(10): 1549-56.
 [http://dx.doi.org/10.1017/S1461145714000510] [PMID: 24786948]

[284]
Cai J, Zhang W, Yi Z, et al. Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive-compulsive symptoms. Psychopharmacology (Berl)  2013; 230(1): 49-55.
 [http://dx.doi.org/10.1007/s00213-013-3137-2] [PMID: 23660601]

[285]
Gisabella B, Bolshakov VY, Benes FM. Kainate receptor-mediated modulation of hippocampal fast spiking interneurons in a rat model of schizophrenia. PLoS One  2012; 7(3): e32483.
 [http://dx.doi.org/10.1371/journal.pone.0032483] [PMID: 22396770]

[286]
Blackwood DH, Thiagarajah T, Malloy P, Pickard BS, Muir WJ. Chromosome abnormalities, mental retardation and the search for genes in bipolar disorder and schizophrenia. Neurotox Res  2008; 14(2-3): 113-20.
 [http://dx.doi.org/10.1007/BF03033803] [PMID: 19073419]

[287]
Schmid SM, Hollmann M. Bridging the synaptic cleft: Lessons from orphan glutamate receptors. Sci Signal  2010; 3(136): pe28.
 [http://dx.doi.org/10.1126/scisignal.3136pe28] [PMID: 20736482]

[288]
Orth A, Tapken D, Hollmann M. The delta subfamily of glutamate receptors: Characterization of receptor chimeras and mutants. Eur J Neurosci  2013; 37(10): 1620-30.
 [http://dx.doi.org/10.1111/ejn.12193] [PMID: 23551821]

[289]
Carrillo E, Gonzalez CU, Berka V, Jayaraman V. Delta glutamate receptors are functional glycine- and ᴅ-serine-gated cation channels in situ. Sci Adv  2021; 7(52): eabk2200.
 [http://dx.doi.org/10.1126/sciadv.abk2200] [PMID: 34936451]

[290]
Lomeli H, Sprengel R, Laurie DJ, et al. The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett  1993; 315(3): 318-22.
 [http://dx.doi.org/10.1016/0014-5793(93)81186-4] [PMID: 8422924]

[291]
Yamazaki M, Araki K, Shibata A, Mishina M. Molecular cloning of a cDNA encoding a novel member of the mouse glutamate receptor channel family. Biochem Biophys Res Commun  1992; 183(2): 886-92.
 [http://dx.doi.org/10.1016/0006-291X(92)90566-4] [PMID: 1372507]

[292]
Yadav R, Gupta SC, Hillman BG, Bhatt JM, Stairs DJ, Dravid SM. Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors. PLoS One  2012; 7(3): e32969.
 [http://dx.doi.org/10.1371/journal.pone.0032969] [PMID: 22412961]

[293]
Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M. Selective expression of the glutamate receptor channel delta 2 subunit in cerebellar purkinje cells. Biochem Biophys Res Commun  1993; 197(3): 1267-76.
 [http://dx.doi.org/10.1006/bbrc.1993.2614] [PMID: 7506541]

[294]
Yuzaki M. Cerebellar LTD vs. motor learning-lessons learned from studying GluD2. Neural Netw  2013; 47: 36-41.
 [http://dx.doi.org/10.1016/j.neunet.2012.07.001] [PMID: 22840919]

[295]
Burada AP, Vinnakota R, Kumar J. The architecture of GluD2 ionotropic delta glutamate receptor elucidated by cryo-EM. J Struct Biol  2020; 211(2): 107546.
 [http://dx.doi.org/10.1016/j.jsb.2020.107546] [PMID: 32512155]

[296]
Burada AP, Vinnakota R, Kumar J. Cryo-EM structures of the ionotropic glutamate receptor GluD1 reveal a non-swapped architecture. Nat Struct Mol Biol  2020; 27(1): 84-91.
 [http://dx.doi.org/10.1038/s41594-019-0359-y] [PMID: 31925409]

[297]
Agulhon C, Fiacco TA, McCarthy KD. Hippocampal short- and long-term plasticity are not modulated by astrocyte Ca2+ signaling. Science  2010; 327(5970): 1250-4.
 [http://dx.doi.org/10.1126/science.1184821] [PMID: 20203048]

[298]
Bartok A, Weaver D, Golenár T, et al. IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer. Nat Commun  2019; 10(1): 3726.
 [http://dx.doi.org/10.1038/s41467-019-11646-3] [PMID: 31427578]

[299]
Foskett JK, White C, Cheung KH, Mak DO. Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev  2007; 87(2): 593-658.
 [http://dx.doi.org/10.1152/physrev.00035.2006] [PMID: 17429043]

[300]
Sharp AH, Nucifora FC Jr, Blondel O, et al. Differential cellular expression of isoforms of inositol 1,4,5-triphosphate receptors in neurons and glia in brain. J Comp Neurol  1999; 406(2): 207-20.
 [http://dx.doi.org/10.1002/(SICI)1096-9861(19990405)406:2<207:::AID-CNE6>3.0.CO;2-7] [PMID: 10096607]

[301]
Shiratori-Hayashi M, Yamaguchi C, Eguchi K, et al. Astrocytic STAT3 activation and chronic itch require IP3R1/TRPC-dependent Ca2+ signals in mice. J Allergy Clin Immunol  2021; 147(4): 1341-53.
 [http://dx.doi.org/10.1016/j.jaci.2020.06.039] [PMID: 32781002]

[302]
Brown SA, Loew LM. Computational analysis of calcium signaling and membrane electrophysiology in cerebellar purkinje neurons associated with ataxia. BMC Syst Biol  2012; 6(1): 70.
 [http://dx.doi.org/10.1186/1752-0509-6-70] [PMID: 22703638]

[303]
Post JI, Leergaard TB, Ratz V, Walaas SI, von Hörsten S, Nissen-Meyer LSH. Differential levels and phosphorylation of type 1 inositol 1,4,5-trisphosphate receptor in four different murine models of Huntington disease. J Huntingtons Dis  2019; 8(3): 271-89.
 [http://dx.doi.org/10.3233/JHD-180301] [PMID: 31256144]

[304]
Sherwood MW, Arizono M, Panatier A, Mikoshiba K, Oliet SHR. Astrocytic IP3Rs: Beyond IP3R2. Front Cell Neurosci  2021; 15: 695817.
 [http://dx.doi.org/10.3389/fncel.2021.695817] [PMID: 34393726]

[305]
Shi M, Chen F, Chen Z, et al. Sigma-1 receptor: A potential therapeutic target for traumatic brain injury. Front Cell Neurosci  2021; 15: 685201.
 [http://dx.doi.org/10.3389/fncel.2021.685201] [PMID: 34658788]

[306]
Bononi A, Giorgi C, Patergnani S, et al. BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature  2017; 546(7659): 549-53.
 [http://dx.doi.org/10.1038/nature22798] [PMID: 28614305]

[307]
Kaczmarek-Hájek K, Lörinczi E, Hausmann R, Nicke A. Molecular and functional properties of P2X receptors--recent progress and persisting challenges. Purinergic Signal  2012; 8(3): 375-417.
 [http://dx.doi.org/10.1007/s11302-012-9314-7] [PMID: 22547202]

[308]
North RA. Molecular physiology of P2X receptors. Physiol Rev  2002; 82(4): 1013-67.
 [http://dx.doi.org/10.1152/physrev.00015.2002] [PMID: 12270951]

[309]
Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev  2007; 87(2): 659-797.
 [http://dx.doi.org/10.1152/physrev.00043.2006] [PMID: 17429044]

[310]
Coddou C, Yan Z, Obsil T, Huidobro-Toro JP, Stojilkovic SS. Activation and regulation of purinergic P2X receptor channels. Pharmacol Rev  2011; 63(3): 641-83.
 [http://dx.doi.org/10.1124/pr.110.003129] [PMID: 21737531]

[311]
Lemoine D, Jiang R, Taly A, Chataigneau T, Specht A, Grutter T. Ligand-gated ion channels: New insights into neurological disorders and ligand recognition. Chem Rev  2012; 112(12): 6285-318.
 [http://dx.doi.org/10.1021/cr3000829] [PMID: 22988962]

[312]
Burnstock G, Fredholm BB, Verkhratsky A. Adenosine and ATP receptors in the brain. Curr Top Med Chem  2011; 11(8): 973-1011.
 [http://dx.doi.org/10.2174/156802611795347627] [PMID: 21401499]

[313]
Bhattacharya A. Recent advances in CNS P2X7 physiology and pharmacology: Focus on neuropsychiatric disorders. Front Pharmacol  2018; 9: 30.
 [http://dx.doi.org/10.3389/fphar.2018.00030] [PMID: 29449810]

[314]
Illes P, Khan TM, Rubini P. Neuronal P2X7 receptors revisited: Do they really exist? J Neurosci  2017; 37(30): 7049-62.
 [http://dx.doi.org/10.1523/JNEUROSCI.3103-16.2017] [PMID: 28747388]

[315]
Calovi S, Mut-Arbona P, Sperlágh B. Microglia and the purinergic signaling system. Neuroscience  2019; 405: 137-47.
 [http://dx.doi.org/10.1016/j.neuroscience.2018.12.021] [PMID: 30582977]

[316]
Kashfi S, Peymani M, Ghaedi K, Baharvand H, Nasr-Esfahani MH, Javan M. Purinergic receptor expression and potential association with human embryonic stem cell-derived oligodendrocyte progenitor cell development. Cell J  2017; 19(3): 386-402.
 [PMID: 28836401]

[317]
Plum T, Wang X, Rettel M, Krijgsveld J, Feyerabend TB, Rodewald HR. Human mast cell proteome reveals unique lineage, putative functions, and structural basis for cell ablation. Immunity  2020; 52(2): 404-416.e5.
 [http://dx.doi.org/10.1016/j.immuni.2020.01.012] [PMID: 32049054]

[318]
Lazarowski ER. Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal  2012; 8(3): 359-73.
 [http://dx.doi.org/10.1007/s11302-012-9304-9] [PMID: 22528679]

[319]
Yamamoto K, Korenaga R, Kamiya A, Qi Z, Sokabe M, Ando J. P2X(4) receptors mediate ATP-induced calcium influx in human vascular endothelial cells. Am J Physiol Heart Circ Physiol  2000; 279(1): H285-92.
 [http://dx.doi.org/10.1152/ajpheart.2000.279.1.H285] [PMID: 10899068]

[320]
Manohar M, Hirsh MI, Chen Y, Woehrle T, Karande AA, Junger WG. ATP release and autocrine signaling through P2X4 receptors regulate γδ T cell activation. J Leukoc Biol  2012; 92(4): 787-94.
 [http://dx.doi.org/10.1189/jlb.0312121] [PMID: 22753954]

[321]
Salter MW, Hicks JL. ATP causes release of intracellular Ca2+ via the phospholipase C beta/IP3 pathway in astrocytes from the dorsal spinal cord. J Neurosci  1995; 15(4): 2961-71.
 [http://dx.doi.org/10.1523/JNEUROSCI.15-04-02961.1995] [PMID: 7722640]

[322]
Cao Q, Zhong XZ, Zou Y, Murrell-Lagnado R, Zhu MX, Dong XP. Calcium release through P2X4 activates calmodulin to promote endolysosomal membrane fusion. J Cell Biol  2015; 209(6): 879-94.
 [http://dx.doi.org/10.1083/jcb.201409071] [PMID: 26101220]

[323]
Jurewicz A, Matysiak M, Tybor K, Kilianek L, Raine CS, Selmaj K. Tumour necrosis factor-induced death of adult human oligodendrocytes is mediated by apoptosis inducing factor. Brain  2005; 128(Pt 11): 2675-88.
 [http://dx.doi.org/10.1093/brain/awh627] [PMID: 16219674]

[324]
Salcman B, Affleck K, Bulfone-Paus S. P2X Receptor-dependent modulation of mast cell and glial cell activities in neuroinflammation. Cells  2021; 10(9): 10.
 [http://dx.doi.org/10.3390/cells10092282] [PMID: 34571930]

[325]
Hendriksen E, van Bergeijk D, Oosting RS, Redegeld FA. Mast cells in neuroinflammation and brain disorders. Neurosci Biobehav Rev  2017; 79: 119-33.
 [http://dx.doi.org/10.1016/j.neubiorev.2017.05.001] [PMID: 28499503]

[326]
Xu J, Zhang X, Qian Q, et al. Histamine upregulates the expression of histamine receptors and increases the neuroprotective effect of astrocytes. J Neuroinflammation  2018; 15(1): 41.
 [http://dx.doi.org/10.1186/s12974-018-1068-x] [PMID: 29433511]

[327]
Jiang L, Cheng L, Chen H, et al. Histamine H2 receptor negatively regulates oligodendrocyte differentiation in neonatal hypoxic-ischemic white matter injury. J Exp Med  2021; 218(1): 218.
 [http://dx.doi.org/10.1084/jem.20191365] [PMID: 32991666]

[328]
James G, Butt AM. P2Y and P2X purinoceptor mediated Ca2+ signalling in glial cell pathology in the central nervous system. Eur J Pharmacol  2002; 447(2-3): 247-60.
 [http://dx.doi.org/10.1016/S0014-2999(02)01756-9] [PMID: 12151016]

[329]
Butt AM, Fern RF, Matute C. Neurotransmitter signaling in white matter. Glia  2014; 62(11): 1762-79.
 [http://dx.doi.org/10.1002/glia.22674] [PMID: 24753049]

[330]
Hamilton N, Vayro S, Kirchhoff F, et al. Mechanisms of ATP- and glutamate-mediated calcium signaling in white matter astrocytes. Glia  2008; 56(7): 734-49.
 [http://dx.doi.org/10.1002/glia.20649] [PMID: 18293404]

[331]
Hamilton N, Vayro S, Wigley R, Butt AM. Axons and astrocytes release ATP and glutamate to evoke calcium signals in NG2-glia. Glia  2010; 58(1): 66-79.
 [http://dx.doi.org/10.1002/glia.20902] [PMID: 19533604]

[332]
Suadicani SO, Brosnan CF, Scemes E. P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J Neurosci  2006; 26(5): 1378-85.
 [http://dx.doi.org/10.1523/JNEUROSCI.3902-05.2006] [PMID: 16452661]

[333]
Allan D, Fairlie-Clarke KJ, Elliott C, et al. Role of IL-33 and ST2 signalling pathway in multiple sclerosis: Expression by oligodendrocytes and inhibition of myelination in central nervous system. Acta Neuropathol Commun  2016; 4(1): 75.
 [http://dx.doi.org/10.1186/s40478-016-0344-1] [PMID: 27455844]

[334]
Martínez-Frailes C, Di Lauro C, Bianchi C, et al. Amyloid peptide induced neuroinflammation increases the P2X7 receptor expression in microglial cells, impacting on its functionality. Front Cell Neurosci  2019; 13: 143.
 [http://dx.doi.org/10.3389/fncel.2019.00143] [PMID: 31031598]

[335]
Martin E, Amar M, Dalle C, et al. New role of P2X7 receptor in an Alzheimer’s disease mouse model. Mol Psychiatry  2019; 24(1): 108-25.
 [http://dx.doi.org/10.1038/s41380-018-0108-3] [PMID: 29934546]

[336]
Sanz JM, Chiozzi P, Ferrari D, et al. Activation of microglia by amyloid beta requires P2X7 receptor expression. J Immunol  2009; 182(7): 4378-85.
 [http://dx.doi.org/10.4049/jimmunol.0803612] [PMID: 19299738]

[337]
Domercq M, Matute C. Targeting P2X4 and P2X7 receptors in multiple sclerosis. Curr Opin Pharmacol  2019; 47: 119-25.
 [http://dx.doi.org/10.1016/j.coph.2019.03.010] [PMID: 31015145]

[338]
D’Ambrosi N, Finocchi P, Apolloni S, et al. The proinflammatory action of microglial P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis. J Immunol  2009; 183(7): 4648-56.
 [http://dx.doi.org/10.4049/jimmunol.0901212] [PMID: 19734218]

[339]
Wang XH, Xie X, Luo XG, Shang H, He ZY. Inhibiting purinergic P2X7 receptors with the antagonist brilliant blue G is neuroprotective in an intranigral lipopolysaccharide animal model of Parkinson’s disease. Mol Med Rep  2017; 15(2): 768-76.
 [http://dx.doi.org/10.3892/mmr.2016.6070] [PMID: 28035410]

[340]
Ribeiro DE, Roncalho AL, Glaser T, Ulrich H, Wegener G, Joca S. P2X7 Receptor signaling in stress and depression. Int J Mol Sci  2019; 20(11): 20.
 [http://dx.doi.org/10.3390/ijms20112778] [PMID: 31174279]

[341]
Wang WZ, Chu XP, Li MH, Seeds J, Simon RP, Xiong ZG. Modulation of acid-sensing ion channel currents, acid-induced increase of intracellular Ca2+, and acidosis-mediated neuronal injury by intracellular pH. J Biol Chem  2006; 281(39): 29369-78.
 [http://dx.doi.org/10.1074/jbc.M605122200] [PMID: 16882660]

[342]
Karsan N, Gonzales EB, Dussor G. Targeted acid-sensing ion channel therapies for migraine. Neurotherapeutics  2018; 15(2): 402-14.
 [http://dx.doi.org/10.1007/s13311-018-0619-2] [PMID: 29549622]

[343]
Wemmie JA, Taugher RJ, Kreple CJ. Acid-sensing ion channels in pain and disease. Nat Rev Neurosci  2013; 14(7): 461-71.
 [http://dx.doi.org/10.1038/nrn3529] [PMID: 23783197]

[344]
Kweon HJ, Suh BC. Acid-sensing ion channels (ASICs): Therapeutic targets for neurological diseases and their regulation. BMB Rep  2013; 46(6): 295-304.
 [http://dx.doi.org/10.5483/BMBRep.2013.46.6.121] [PMID: 23790972]

[345]
Chu XP, Xiong ZG. Physiological and pathological functions of acid-sensing ion channels in the central nervous system. Curr Drug Targets  2012; 13(2): 263-71.
 [http://dx.doi.org/10.2174/138945012799201685] [PMID: 22204324]

[346]
Sluka KA, Winter OC, Wemmie JA. Acid-sensing ion channels: A new target for pain and CNS diseases. Curr Opin Drug Discov Devel  2009; 12(5): 693-704.
 [PMID: 19736627]

[347]
Deval E, Gasull X, Noël J, et al. Acid-sensing ion channels (ASICs): Pharmacology and implication in pain. Pharmacol Ther  2010; 128(3): 549-58.
 [http://dx.doi.org/10.1016/j.pharmthera.2010.08.006] [PMID: 20807551]

[348]
Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M. A proton-gated cation channel involved in acid-sensing. Nature  1997; 386(6621): 173-7.
 [http://dx.doi.org/10.1038/386173a0] [PMID: 9062189]

[349]
Uchitel OD, González Inchauspe C, Weissmann C. Synaptic signals mediated by protons and acid-sensing ion channels. Synapse  2019; 73(10): e22120.
 [http://dx.doi.org/10.1002/syn.22120] [PMID: 31180161]

[350]
Gründer S, Chen X. Structure, function, and pharmacology of acid-sensing ion channels (ASICs): Focus on ASIC1a. Int J Physiol Pathophysiol Pharmacol  2010; 2(2): 73-94.
 [PMID: 21383888]

[351]
Zha XM. Acid-sensing ion channels: Trafficking and synaptic function. Mol Brain  2013; 6(1): 1.
 [http://dx.doi.org/10.1186/1756-6606-6-1] [PMID: 23281934]

[352]
Sherwood TW, Lee KG, Gormley MG, Askwith CC. Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death. J Neurosci  2011; 31(26): 9723-34.
 [http://dx.doi.org/10.1523/JNEUROSCI.1665-11.2011] [PMID: 21715637]

[353]
Yoder N, Yoshioka C, Gouaux E. Gating mechanisms of acid-sensing ion channels. Nature  2018; 555(7696): 397-401.
 [http://dx.doi.org/10.1038/nature25782] [PMID: 29513651]

[354]
Hesselager M, Timmermann DB, Ahring PK. pH Dependency and desensitization kinetics of heterologously expressed combinations of acid-sensing ion channel subunits. J Biol Chem  2004; 279(12): 11006-15.
 [http://dx.doi.org/10.1074/jbc.M313507200] [PMID: 14701823]

[355]
Zhang P, Sigworth FJ, Canessa CM. Gating of acid-sensitive ion channel-1: Release of Ca2+ block vs. allosteric mechanism. J Gen Physiol  2006; 127(2): 109-17.
 [http://dx.doi.org/10.1085/jgp.200509396] [PMID: 16418400]

[356]
Bhalla V, Hallows KR. Mechanisms of ENaC regulation and clinical implications. J Am Soc Nephrol  2008; 19(10): 1845-54.
 [http://dx.doi.org/10.1681/ASN.2008020225] [PMID: 18753254]

[357]
Sharma K, Haque M, Guidry R, Ueta Y, Teruyama R. Effect of dietary salt intake on epithelial Na+ channels (ENaC) in vasopressin magnocellular neurosecretory neurons in the rat supraoptic nucleus. J Physiol  2017; 595(17): 5857-74.
 [http://dx.doi.org/10.1113/JP274856] [PMID: 28714095]

[358]
Schild L. The epithelial sodium channel: From molecule to disease. Rev Physiol Biochem Pharmacol  2004; 151: 93-107.
 [http://dx.doi.org/10.1007/s10254-004-0023-7] [PMID: 15146350]

[359]
Blakemore LJ, Trombley PQ. Zinc as a neuromodulator in the central nervous system with a focus on the olfactory bulb. Front Cell Neurosci  2017; 11: 297.
 [http://dx.doi.org/10.3389/fncel.2017.00297] [PMID: 29033788]

[360]
Assaf SY, Chung SH. Release of endogenous Zn2+ from brain tissue during activity. Nature  1984; 308(5961): 734-6.
 [http://dx.doi.org/10.1038/308734a0] [PMID: 6717566]

[361]
Howell GA, Welch MG, Frederickson CJ. Stimulation-induced uptake and release of zinc in hippocampal slices. Nature  1984; 308(5961): 736-8.
 [http://dx.doi.org/10.1038/308736a0] [PMID: 6717567]

[362]
Davies PA, Wang W, Hales TG, Kirkness EF. A novel class of ligand-gated ion channel is activated by Zn2+. J Biol Chem  2003; 278(2): 712-7.
 [http://dx.doi.org/10.1074/jbc.M208814200] [PMID: 12381728]

[363]
Houtani T, Munemoto Y, Kase M, Sakuma S, Tsutsumi T, Sugimoto T. Cloning and expression of ligand-gated ion-channel receptor L2 in central nervous system. Biochem Biophys Res Commun  2005; 335(2): 277-85.
 [http://dx.doi.org/10.1016/j.bbrc.2005.07.079] [PMID: 16083862]

[364]
Rivers-Auty J, Tapia VS, White CS, et al. Zinc status alters Alzheimer’s disease progression through NLRP3-dependent inflammation. J Neurosci  2021; 41(13): 3025-38.
 [http://dx.doi.org/10.1523/JNEUROSCI.1980-20.2020] [PMID: 33597269]

[365]
D’Amico E, Grosso G, Nieves JW, Zanghì A, Factor-Litvak P, Mitsumoto H. Metabolic abnormalities, dietary risk factors and nutritional management in amyotrophic lateral sclerosis. Nutrients  2021; 13(7): 13.
 [http://dx.doi.org/10.3390/nu13072273] [PMID: 34209133]

[366]
Alexander SPH, Fabbro D, Kelly E, et al. CGTP Collaborators. The concise guide to pharmacology 2019/20: Enzymes. Br J Pharmacol  2019; 176 (Suppl. 1): S297-396.
 [http://dx.doi.org/10.1111/bph.14752] [PMID: 31710714]

[367]
Dey A, Allen JN, Fraser JW, et al. Neuroprotective role of the ron receptor tyrosine kinase underlying central nervous system inflammation in health and disease. Front Immunol  2018; 9: 513.
 [http://dx.doi.org/10.3389/fimmu.2018.00513] [PMID: 29616029]

[368]
Yu S, Allen JN, Dey A, et al. The ron receptor tyrosine kinase regulates macrophage heterogeneity and plays a protective role in diet-induced obesity, atherosclerosis, and hepatosteatosis. J Immunol  2016; 197(1): 256-65.
 [http://dx.doi.org/10.4049/jimmunol.1600450] [PMID: 27233965]

[369]
Li J, Halfter K, Zhang M, et al. Computational analysis of receptor tyrosine kinase inhibitors and cancer metabolism: Implications for treatment and discovery of potential therapeutic signatures. BMC Cancer  2019; 19(1): 600.
 [http://dx.doi.org/10.1186/s12885-019-5804-0] [PMID: 31208363]

[370]
Robinson DR, Wu YM, Lin SF. The protein tyrosine kinase family of the human genome. Oncogene  2000; 19(49): 5548-57.
 [http://dx.doi.org/10.1038/sj.onc.1203957] [PMID: 11114734]

[371]
van der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol  1994; 10(1): 251-337.
 [http://dx.doi.org/10.1146/annurev.cb.10.110194.001343] [PMID: 7888178]

[372]
Hirai H, Maru Y, Hagiwara K, Nishida J, Takaku F. A novel putative tyrosine kinase receptor encoded by the eph gene. Science  1987; 238(4834): 1717-20.
 [http://dx.doi.org/10.1126/science.2825356] [PMID: 2825356]

[373]
Klein R. Bidirectional modulation of synaptic functions by Eph/ephrin signaling. Nat Neurosci  2009; 12(1): 15-20.
 [http://dx.doi.org/10.1038/nn.2231] [PMID: 19029886]

[374]
Stallaert W, Brüggemann Y, Sabet O, Baak L, Gattiglio M, Bastiaens PIH. Contact inhibitory Eph signaling suppresses EGF-promoted cell migration by decoupling EGFR activity from vesicular recycling. Sci Signal  2018; 11(541): 11.
 [http://dx.doi.org/10.1126/scisignal.aat0114] [PMID: 30065026]

[375]
Coulthard MG, Morgan M, Woodruff TM, et al. Eph/Ephrin signaling in injury and inflammation. Am J Pathol  2012; 181(5): 1493-503.
 [http://dx.doi.org/10.1016/j.ajpath.2012.06.043] [PMID: 23021982]

[376]
Fabes J, Anderson P, Brennan C, Bolsover S. Regeneration-enhancing effects of EphA4 blocking peptide following corticospinal tract injury in adult rat spinal cord. Eur J Neurosci  2007; 26(9): 2496-505.
 [http://dx.doi.org/10.1111/j.1460-9568.2007.05859.x] [PMID: 17970742]

[377]
Casalini P, Iorio MV, Galmozzi E, Ménard S. Role of HER receptors family in development and differentiation. J Cell Physiol  2004; 200(3): 343-50.
 [http://dx.doi.org/10.1002/jcp.20007] [PMID: 15254961]

[378]
Duchnowska R, Loibl S, Jassem J. Tyrosine kinase inhibitors for brain metastases in HER2-positive breast cancer. Cancer Treat Rev  2018; 67: 71-7.
 [http://dx.doi.org/10.1016/j.ctrv.2018.05.004] [PMID: 29772459]

[379]
Aiko N, Shimokawa T, Miyazaki K, et al. Comparison of the efficacies of first-generation epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in patients with advanced non-small-cell lung cancer harboring EGFR mutations. BMC Cancer  2018; 18(1): 1012.
 [http://dx.doi.org/10.1186/s12885-018-4911-7] [PMID: 30348116]

[380]
Zeng Q, Wang J, Cheng Z, et al. Discovery and evaluation of clinical candidate AZD3759, a potent, oral active, central nervous system-penetrant, epidermal growth factor receptor tyrosine kinase inhibitor. J Med Chem  2015; 58(20): 8200-15.
 [http://dx.doi.org/10.1021/acs.jmedchem.5b01073] [PMID: 26313252]

[381]
Matrone C, Marolda R, Ciafrè S, Ciotti MT, Mercanti D, Calissano P. Tyrosine kinase nerve growth factor receptor switches from prosurvival to proapoptotic activity via abeta-mediated phosphorylation. Proc Natl Acad Sci USA  2009; 106(27): 11358-63.
 [http://dx.doi.org/10.1073/pnas.0904998106] [PMID: 19549834]

[382]
Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: From the early discoveries to the potential clinical use. J Transl Med  2012; 10(1): 239.
 [http://dx.doi.org/10.1186/1479-5876-10-239] [PMID: 23190582]

[383]
Mufson EJ, Counts SE, Ginsberg SD, et al. Nerve growth factor pathobiology during the progression of Alzheimer’s disease. Front Neurosci  2019; 13: 533.
 [http://dx.doi.org/10.3389/fnins.2019.00533] [PMID: 31312116]

[384]
Cheng HC, Sun Y, Lai LC, et al. Genetic polymorphisms of nerve growth factor receptor (NGFR) and the risk of Alzheimer’s disease. J Negat Results Biomed  2012; 11(1): 5.
 [http://dx.doi.org/10.1186/1477-5751-11-5] [PMID: 22236693]

[385]
Skaper SD. The biology of neurotrophins, signalling pathways, and functional peptide mimetics of neurotrophins and their receptors. CNS Neurol Disord Drug Targets  2008; 7(1): 46-62.
 [http://dx.doi.org/10.2174/187152708783885174] [PMID: 18289031]

[386]
Huang EJ, Reichardt LF. Trk receptors: Roles in neuronal signal transduction. Annu Rev Biochem  2003; 72(1): 609-42.
 [http://dx.doi.org/10.1146/annurev.biochem.72.121801.161629] [PMID: 12676795]

[387]
Bernal J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab  2007; 3(3): 249-59.
 [http://dx.doi.org/10.1038/ncpendmet0424] [PMID: 17315033]

[388]
Roux PP, Barker PA. Neurotrophin signaling through the p75 neurotrophin receptor. Prog Neurobiol  2002; 67(3): 203-33.
 [http://dx.doi.org/10.1016/S0301-0082(02)00016-3] [PMID: 12169297]

[389]
Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell  2010; 141(7): 1117-34.
 [http://dx.doi.org/10.1016/j.cell.2010.06.011] [PMID: 20602996]

[390]
Yu J, Rupasinghe C, Wilson JL, et al. Targeting receptor tyrosine kinases and their downstream signaling with cell-penetrating peptides in human pulmonary artery smooth muscle and endothelial cells. Chem Biol Drug Des  2015; 85(5): 586-97.
 [http://dx.doi.org/10.1111/cbdd.12446] [PMID: 25298192]

[391]
Reuss B, von Bohlen und Halbach O. Fibroblast growth factors and their receptors in the central nervous system. Cell Tissue Res  2003; 313(2): 139-57.
 [http://dx.doi.org/10.1007/s00441-003-0756-7] [PMID: 12845521]

[392]
Ornitz DM, Xu J, Colvin JS, et al. Receptor specificity of the fibroblast growth factor family. J Biol Chem  1996; 271(25): 15292-7.
 [http://dx.doi.org/10.1074/jbc.271.25.15292] [PMID: 8663044]

[393]
Klimaschewski L, Claus P. Fibroblast growth factor signalling in the diseased nervous system. Mol Neurobiol  2021; 58(8): 3884-902.
 [http://dx.doi.org/10.1007/s12035-021-02367-0] [PMID: 33860438]

[394]
Sarabipour S, Hristova K. Mechanism of FGF receptor dimerization and activation. Nat Commun  2016; 7(1): 10262.
 [http://dx.doi.org/10.1038/ncomms10262] [PMID: 26725515]

[395]
Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev  2005; 16(2): 139-49.
 [http://dx.doi.org/10.1016/j.cytogfr.2005.01.001] [PMID: 15863030]

[396]
Airaksinen MS, Saarma M. The GDNF family: Signalling, biological functions and therapeutic value. Nat Rev Neurosci  2002; 3(5): 383-94.
 [http://dx.doi.org/10.1038/nrn812] [PMID: 11988777]

[397]
Runeberg-Roos P, Saarma M. Neurotrophic factor receptor RET: Structure, cell biology, and inherited diseases. Ann Med  2007; 39(8): 572-80.
 [http://dx.doi.org/10.1080/07853890701646256] [PMID: 17934909]

[398]
Schlee S, Carmillo P, Whitty A. Quantitative analysis of the activation mechanism of the multicomponent growth-factor receptor Ret. Nat Chem Biol  2006; 2(11): 636-44.
 [http://dx.doi.org/10.1038/nchembio823] [PMID: 17013378]

[399]
Werner H, LeRoith D. Insulin and insulin-like growth factor receptors in the brain: Physiological and pathological aspects. Eur Neuropsychopharmacol  2014; 24(12): 1947-53.
 [http://dx.doi.org/10.1016/j.euroneuro.2014.01.020] [PMID: 24529663]

[400]
Gammeltoft S, Haselbacher GK, Humbel RE, Fehlmann M, Van Obberghen E. Two types of receptor for insulin-like growth factors in mammalian brain. EMBO J  1985; 4(13A): 3407-12.
 [http://dx.doi.org/10.1002/j.1460-2075.1985.tb04097.x] [PMID: 3004958]

[401]
Shaw LM. The insulin receptor substrate (IRS) proteins: At the intersection of metabolism and cancer. Cell Cycle  2011; 10(11): 1750-6.
 [http://dx.doi.org/10.4161/cc.10.11.15824] [PMID: 21597332]

[402]
Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: More than just a peripheral hormone. J Aging Res  2012; 2012: 384017.
 [http://dx.doi.org/10.1155/2012/384017] [PMID: 22500228]

[403]
Feld GB, Wilhem I, Benedict C, et al. Central nervous insulin signaling in sleep-associated memory formation and neuroendocrine regulation. Neuropsychopharmacology  2016; 41(6): 1540-50.
 [http://dx.doi.org/10.1038/npp.2015.312] [PMID: 26448203]

[404]
Sheehan TP, Neve RL, Duman RS, Russell DS. Antidepressant effect of the calcium-activated tyrosine kinase Pyk2 in the lateral septum. Biol Psychiatry  2003; 54(5): 540-51.
 [http://dx.doi.org/10.1016/S0006-3223(02)01815-2] [PMID: 12946883]

[405]
Menegon A, Burgaya F, Baudot P, Dunlap DD, Girault JA, Valtorta F. FAK+ and PYK2/CAKbeta, two related tyrosine kinases highly expressed in the central nervous system: Similarities and differences in the expression pattern. Eur J Neurosci  1999; 11(11): 3777-88.
 [http://dx.doi.org/10.1046/j.1460-9568.1999.00798.x] [PMID: 10583467]

[406]
Tian D, Litvak V, Lev S. Cerebral ischemia and seizures induce tyrosine phosphorylation of PYK2 in neurons and microglial cells. J Neurosci  2000; 20(17): 6478-87.
 [http://dx.doi.org/10.1523/JNEUROSCI.20-17-06478.2000] [PMID: 10964954]

[407]
de Pins B, Mendes T, Giralt A, Girault JA. The non-receptor tyrosine kinase Pyk2 in brain function and neurological and psychiatric diseases. Front Synaptic Neurosci  2021; 13: 749001.
 [http://dx.doi.org/10.3389/fnsyn.2021.749001] [PMID: 34690733]

[408]
Kohno T, Matsuda E, Sasaki H, Sasaki T. Protein-tyrosine kinase CAKbeta/PYK2 is activated by binding Ca2+/calmodulin to FERM F2 alpha2 helix and thus forming its dimer. Biochem J  2008; 410(3): 513-23.
 [http://dx.doi.org/10.1042/BJ20070665] [PMID: 18031286]

[409]
Niimura M, Moussa R, Bissoon N, Ikeda-Douglas C, Milgram NW, Gurd JW. Changes in phosphorylation of the NMDA receptor in the rat hippocampus induced by status epilepticus. J Neurochem  2005; 92(6): 1377-85.
 [http://dx.doi.org/10.1111/j.1471-4159.2005.02977.x] [PMID: 15748156]

[410]
Sun Y, Savanenin A, Reddy PH, Liu YF. Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-D-aspartate receptors via post-synaptic density 95. J Biol Chem  2001; 276(27): 24713-8.
 [http://dx.doi.org/10.1074/jbc.M103501200] [PMID: 11319238]

[411]
Lambert JC, Ibrahim-Verbaas CA, Harold D, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet  2013; 45(12): 1452-8.
 [http://dx.doi.org/10.1038/ng.2802] [PMID: 24162737]

[412]
Alexander SPH, Cidlowski JA, Kelly E, et al. CGTP Collaborators. The concise guide to pharmacology 2019/20: Nuclear hormone receptors. Br J Pharmacol  2019; 176 (Suppl. 1): S229-46.
 [http://dx.doi.org/10.1111/bph.14750] [PMID: 31710718]

[413]
Ferrara SJ, Scanlan TS. A CNS-targeting prodrug strategy for nuclear receptor modulators. J Med Chem  2020; 63(17): 9742-51.
 [http://dx.doi.org/10.1021/acs.jmedchem.0c00868] [PMID: 32787092]

[414]
Moutinho M, Codocedo JF, Puntambekar SS, Landreth GE. Nuclear receptors as therapeutic targets for neurodegenerative diseases: Lost in translation. Annu Rev Pharmacol Toxicol  2019; 59(1): 237-61.
 [http://dx.doi.org/10.1146/annurev-pharmtox-010818-021807] [PMID: 30208281]

[415]
Kim CH, Han BS, Moon J, et al. Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. Proc Natl Acad Sci USA  2015; 112(28): 8756-61.
 [http://dx.doi.org/10.1073/pnas.1509742112] [PMID: 26124091]

[416]
Kabat GC, Etgen AM, Rohan TE. Do steroid hormones play a role in the etiology of glioma? Cancer Epidemiol Biomarkers Prev  2010; 19(10): 2421-7.
 [http://dx.doi.org/10.1158/1055-9965.EPI-10-0658] [PMID: 20841389]

[417]
Xu Y, O’Malley BW, Elmquist JK. Brain nuclear receptors and body weight regulation. J Clin Invest  2017; 127(4): 1172-80.
 [http://dx.doi.org/10.1172/JCI88891] [PMID: 28218618]

[418]
Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov  2006; 5(12): 993-6.
 [http://dx.doi.org/10.1038/nrd2199] [PMID: 17139284]

[419]
Moore JT, Collins JL, Pearce KH. The nuclear receptor superfamily and drug discovery. ChemMedChem  2006; 1(5): 504-23.
 [http://dx.doi.org/10.1002/cmdc.200600006] [PMID: 16892386]

[420]
Sladek FM. What are nuclear receptor ligands? Mol Cell Endocrinol  2011; 334(1-2): 3-13.
 [http://dx.doi.org/10.1016/j.mce.2010.06.018] [PMID: 20615454]

[421]
Xu EH, Lambert MH. Structural insights into regulation of nuclear receptors by ligands. Nucl Recept Signal  2003; 1(1): e004.
 [http://dx.doi.org/10.1621/nrs.01004] [PMID: 16604176]

[422]
Park J, Kim CH. Regulation of common neurological disorders by gut microbial metabolites. Exp Mol Med  2021; 53(12): 1821-33.
 [http://dx.doi.org/10.1038/s12276-021-00703-x] [PMID: 34857900]

[423]
McMillin M, DeMorrow S. Effects of bile acids on neurological function and disease. FASEB J  2016; 30(11): 3658-68.
 [http://dx.doi.org/10.1096/fj.201600275R] [PMID: 27468758]

[424]
Sarkar A, Carter EL, Harland JB, Speelman AL, Lehnert N, Ragsdale SW. Ferric heme as a CO/NO sensor in the nuclear receptor Rev-Erbß by coupling gas binding to electron transfer. Proc Natl Acad Sci USA  2021; 118(3): 118.
 [http://dx.doi.org/10.1073/pnas.2016717118] [PMID: 33436410]

[425]
Raghuram S, Stayrook KR, Huang P, et al. Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta. Nat Struct Mol Biol  2007; 14(12): 1207-13.
 [http://dx.doi.org/10.1038/nsmb1344] [PMID: 18037887]

[426]
Jeong H, Moye LS, Southey BR, et al. Gene network dysregulation in the trigeminal ganglia and nucleus accumbens of a model of chronic migraine-associated hyperalgesia. Front Syst Neurosci  2018; 12: 63.
 [http://dx.doi.org/10.3389/fnsys.2018.00063] [PMID: 30618656]

[427]
Gupta S, McCarson KE, Welch KM, Berman NE. Mechanisms of pain modulation by sex hormones in migraine. Headache  2011; 51(6): 905-22.
 [http://dx.doi.org/10.1111/j.1526-4610.2011.01908.x] [PMID: 21631476]

[428]
Levy D, Jakubowski M, Burstein R. Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists. Proc Natl Acad Sci USA  2004; 101(12): 4274-9.
 [http://dx.doi.org/10.1073/pnas.0306147101] [PMID: 15016917]

[429]
Zhang C, Zhang B, Zhang X, Sun G, Sun X. Targeting orphan nuclear receptors NR4As for energy homeostasis and diabetes. Front Pharmacol  2020; 11: 587457.
 [http://dx.doi.org/10.3389/fphar.2020.587457] [PMID: 33328994]

[430]
Tobin JF, Freedman LP. Nuclear receptors as drug targets in metabolic diseases: New approaches to therapy. Trends Endocrinol Metab  2006; 17(7): 284-90.
 [http://dx.doi.org/10.1016/j.tem.2006.07.004] [PMID: 16870465]

[431]
Kong Y, Zhou W, Sun Z. Nuclear receptor corepressors in intellectual disability and autism. Mol Psychiatry  2020; 25(10): 2220-36.
 [http://dx.doi.org/10.1038/s41380-020-0667-y] [PMID: 32034290]

[432]
Jang Y, Kim W, Leblanc P, Kim CH, Kim KS. Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1. Exp Mol Med  2021; 53(1): 19-29.
 [http://dx.doi.org/10.1038/s12276-021-00555-5] [PMID: 33479411]

[433]
Casali BT, Reed-Geaghan EG, Landreth GE. Nuclear receptor agonist-driven modification of inflammation and amyloid pathology enhances and sustains cognitive improvements in a mouse model of Alzheimer’s disease. J Neuroinflammation  2018; 15(1): 43.
 [http://dx.doi.org/10.1186/s12974-018-1091-y] [PMID: 29448961]

[434]
Moutinho M, Landreth GE. Therapeutic potential of nuclear receptor agonists in Alzheimer’s disease. J Lipid Res  2017; 58(10): 1937-49.
 [http://dx.doi.org/10.1194/jlr.R075556] [PMID: 28264880]

[435]
Wada Y, Maekawa M, Ohnishi T, et al. Peroxisome proliferator-activated receptor α as a novel therapeutic target for schizophrenia. EBioMedicine  2020; 62: 103130.
 [http://dx.doi.org/10.1016/j.ebiom.2020.103130] [PMID: 33279456]

[436]
Tsai SY, Catts VS, Fullerton JM, Corley SM, Fillman SG, Weickert CS. Nuclear receptors and neuroinflammation in schizophrenia. Mol Neuropsychiatry  2018; 3(4): 181-91.
 [http://dx.doi.org/10.1159/000485565] [PMID: 29888229]

[437]
Dwyer JB, Aftab A, Radhakrishnan R, et al. APA Council of Research Task Force on Novel Biomarkers and Treatments. Hormonal treatments for major depressive disorder: State of the art. Am J Psychiatry  2020; 177(8): 686-705.
 [http://dx.doi.org/10.1176/appi.ajp.2020.19080848] [PMID: 32456504]

[438]
Skerrett R, Malm T, Landreth G. Nuclear receptors in neurodegenerative diseases. Neurobiol Dis  2014; 72(Pt A): 104-16.
 [http://dx.doi.org/10.1016/j.nbd.2014.05.019]

[439]
Huang P, Chandra V, Rastinejad F. Structural overview of the nuclear receptor superfamily: Insights into physiology and therapeutics. Annu Rev Physiol  2010; 72(1): 247-72.
 [http://dx.doi.org/10.1146/annurev-physiol-021909-135917] [PMID: 20148675]

[440]
Bain DL, Heneghan AF, Connaghan-Jones KD, Miura MT. Nuclear receptor structure: Implications for function. Annu Rev Physiol  2007; 69(1): 201-20.
 [http://dx.doi.org/10.1146/annurev.physiol.69.031905.160308] [PMID: 17137423]

[441]
Rastinejad F, Huang P, Chandra V, Khorasanizadeh S. Understanding nuclear receptor form and function using structural biology. J Mol Endocrinol  2013; 51(3): T1-T21.
 [http://dx.doi.org/10.1530/JME-13-0173] [PMID: 24103914]

[442]
Kumar R, Thompson EB. Transactivation functions of the N-terminal domains of nuclear hormone receptors: Protein folding and coactivator interactions. Mol Endocrinol  2003; 17(1): 1-10.
 [http://dx.doi.org/10.1210/me.2002-0258] [PMID: 12511601]

[443]
Anbalagan M, Huderson B, Murphy L, Rowan BG. Post-translational modifications of nuclear receptors and human disease. Nucl Recept Signal  2012; 10(1): e001.
 [http://dx.doi.org/10.1621/nrs.10001] [PMID: 22438791]

[444]
Gronemeyer H, Moras D. Nuclear receptors. How to finger DNA. Nature  1995; 375(6528): 190-1.
 [http://dx.doi.org/10.1038/375190a0] [PMID: 7746310]

[445]
Rastinejad F, Perlmann T, Evans RM, Sigler PB. Structural determinants of nuclear receptor assembly on DNA direct repeats. Nature  1995; 375(6528): 203-11.
 [http://dx.doi.org/10.1038/375203a0] [PMID: 7746322]

[446]
Pawlak M, Lefebvre P, Staels B. General molecular biology and architecture of nuclear receptors. Curr Top Med Chem  2012; 12(6): 486-504.
 [http://dx.doi.org/10.2174/156802612799436641] [PMID: 22242852]

[447]
Wurtz JM, Bourguet W, Renaud JP, et al. A canonical structure for the ligand-binding domain of nuclear receptors. Nat Struct Biol  1996; 3(1): 87-94.
 [http://dx.doi.org/10.1038/nsb0196-87] [PMID: 8548460]

[448]
Solomon IH, Hager JM, Safi R, McDonnell DP, Redinbo MR, Ortlund EA. Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity. J Mol Biol  2005; 354(5): 1091-102.
 [http://dx.doi.org/10.1016/j.jmb.2005.10.009] [PMID: 16289203]

[449]
Weatherman RV, Fletterick RJ, Scanlan TS. Nuclear-receptor ligands and ligand-binding domains. Annu Rev Biochem  1999; 68(1): 559-81.
 [http://dx.doi.org/10.1146/annurev.biochem.68.1.559] [PMID: 10872460]

[450]
Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: Structure and function. Curr Opin Cell Biol  1998; 10(3): 384-91.
 [http://dx.doi.org/10.1016/S0955-0674(98)80015-X] [PMID: 9640540]

[451]
Heery DM, Kalkhoven E, Hoare S, Parker MG. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature  1997; 387(6634): 733-6.
 [http://dx.doi.org/10.1038/42750] [PMID: 9192902]

[452]
Seol W, Choi HS, Moore DD. An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors. Science  1996; 272(5266): 1336-9.
 [http://dx.doi.org/10.1126/science.272.5266.1336] [PMID: 8650544]

[453]
Ortlund EA, Lee Y, Solomon IH, et al. Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP. Nat Struct Mol Biol  2005; 12(4): 357-63.
 [http://dx.doi.org/10.1038/nsmb910] [PMID: 15723037]

[454]
Nedumaran B, Kim GS, Hong S, et al. Orphan nuclear receptor DAX-1 acts as a novel corepressor of liver X receptor alpha and inhibits hepatic lipogenesis. J Biol Chem  2010; 285(12): 9221-32.
 [http://dx.doi.org/10.1074/jbc.M109.073650] [PMID: 20080977]

[455]
Weikum ER, Liu X, Ortlund EA. The nuclear receptor superfamily: A structural perspective. Protein Sci  2018; 27(11): 1876-92.
 [http://dx.doi.org/10.1002/pro.3496] [PMID: 30109749]

[456]
Novac N, Heinzel T. Nuclear receptors: Overview and classification. Curr Drug Targets Inflamm Allergy  2004; 3(4): 335-46.
 [http://dx.doi.org/10.2174/1568010042634541] [PMID: 15584884]

[457]
Germain P, Staels B, Dacquet C, Spedding M, Laudet V. Overview of nomenclature of nuclear receptors. Pharmacol Rev  2006; 58(4): 685-704.
 [http://dx.doi.org/10.1124/pr.58.4.2] [PMID: 17132848]

[458]
Nuclear Receptors Nomenclature Committee. A unified nomenclature system for the nuclear receptor superfamily. Cell  1999; 97(2): 161-3.
 [http://dx.doi.org/10.1016/S0092-8674(00)80726-6] [PMID: 10219237]

[459]
Escriva H, Delaunay F, Laudet V. Ligand binding and nuclear receptor evolution. BioEssays  2000; 22(8): 717-27.
 [http://dx.doi.org/10.1002/1521-1878(200008)22:8<717::AID-BIES5>3.0.CO;2-I] [PMID: 10918302]

[460]
Thornton JW, DeSalle R. A new method to localize and test the significance of incongruence: Detecting domain shuffling in the nuclear receptor superfamily. Syst Biol  2000; 49(2): 183-201.
 [http://dx.doi.org/10.1093/sysbio/49.2.183] [PMID: 12118404]

[461]
Suntharalingham JP, Buonocore F, Duncan AJ, Achermann JC. DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best Pract Res Clin Endocrinol Metab  2015; 29(4): 607-19.
 [http://dx.doi.org/10.1016/j.beem.2015.07.004] [PMID: 26303087]

[462]
Timiras PS. Distribution, development and function of thyroid hormone receptors in the brain. Proc West Pharmacol Soc  1979; 22: 371-4.
 [PMID: 229491]

[463]
Lane MA, Bailey SJ. Role of retinoid signalling in the adult brain. Prog Neurobiol  2005; 75(4): 275-93.
 [http://dx.doi.org/10.1016/j.pneurobio.2005.03.002] [PMID: 15882777]

[464]
Fragoso YD, Shearer KD, Sementilli A, de Carvalho LV, McCaffery PJ. High expression of retinoic acid receptors and synthetic enzymes in the human hippocampus. Brain Struct Funct  2012; 217(2): 473-83.
 [http://dx.doi.org/10.1007/s00429-011-0359-0] [PMID: 22075950]

[465]
Warden A, Truitt J, Merriman M, et al. Localization of PPAR isotypes in the adult mouse and human brain. Sci Rep  2016; 6(1): 27618.
 [http://dx.doi.org/10.1038/srep27618] [PMID: 27283430]

[466]
Kojetin DJ, Burris TP. REV-ERB and ROR nuclear receptors as drug targets. Nat Rev Drug Discov  2014; 13(3): 197-216.
 [http://dx.doi.org/10.1038/nrd4100] [PMID: 24577401]

[467]
Cook DN, Kang HS, Jetten AM. Retinoic acid-related orphan receptors (RORs): Regulatory functions in immunity, development, circadian rhythm, and metabolism. Nucl Receptor Res  2015; 2: 2.
 [http://dx.doi.org/10.11131/2015/101185] [PMID: 26878025]

[468]
Huang C, Wang J, Hu W, et al. Identification of functional farnesoid X receptors in brain neurons. FEBS Lett  2016; 590(18): 3233-42.
 [http://dx.doi.org/10.1002/1873-3468.12373] [PMID: 27545319]

[469]
Hucke S, Herold M, Liebmann M, et al. The farnesoid-X-receptor in myeloid cells controls CNS autoimmunity in an IL-10-dependent fashion. Acta Neuropathol  2016; 132(3): 413-31.
 [http://dx.doi.org/10.1007/s00401-016-1593-6] [PMID: 27383204]

[470]
Wang L, Schuster GU, Hultenby K, Zhang Q, Andersson S, Gustafsson JA. Liver X receptors in the central nervous system: From lipid homeostasis to neuronal degeneration. Proc Natl Acad Sci USA  2002; 99(21): 13878-83.
 [http://dx.doi.org/10.1073/pnas.172510899] [PMID: 12368482]

[471]
Lee PW, Selhorst A, Lampe SG, Liu Y, Yang Y, Lovett-Racke AE. Neuron-specific vitamin D signaling attenuates microglia activation and CNS autoimmunity. Front Neurol  2020; 11: 19.
 [http://dx.doi.org/10.3389/fneur.2020.00019] [PMID: 32082243]

[472]
Huang JK, Jarjour AA, Nait Oumesmar B, et al. Retinoid X receptor gamma signaling accelerates CNS remyelination. Nat Neurosci  2011; 14(1): 45-53.
 [http://dx.doi.org/10.1038/nn.2702] [PMID: 21131950]

[473]
Dawson MI, Xia Z. The retinoid X receptors and their ligands. Biochim Biophys Acta  2012; 1821(1): 21-56.
 [http://dx.doi.org/10.1016/j.bbalip.2011.09.014] [PMID: 22020178]

[474]
Anderson GW, Larson RJ, Oas DR, et al. Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) modulates expression of the purkinje cell protein-2 gene. A potential role for COUP-TF in repressing premature thyroid hormone action in the developing brain. J Biol Chem  1998; 273(26): 16391-9.
 [http://dx.doi.org/10.1074/jbc.273.26.16391] [PMID: 9632703]

[475]
Qiu Y, Krishnan V, Pereira FA, Tsai SY, Tsai MJ. Chicken ovalbumin upstream promoter-transcription factors and their regulation. J Steroid Biochem Mol Biol  1996; 56(1-6 Spec No): 81-5.
 [http://dx.doi.org/10.1016/0960-0760(95)00225-1] [PMID: 8603050]

[476]
Yamanishi K, Doe N, Sumida M, et al. Hepatocyte nuclear factor 4 alpha is a key factor related to depression and physiological homeostasis in the mouse brain. PLoS One  2015; 10(3): e0119021.
 [http://dx.doi.org/10.1371/journal.pone.0119021] [PMID: 25774879]

[477]
Wilson TE, Fahrner TJ, Milbrandt J. The orphan receptors NGFIB and steroidogenic factor 1 establish monomer binding as a third paradigm of nuclear receptor-DNA interaction. Mol Cell Biol  1993; 13(9): 5794-804.
 [PMID: 8395013]

[478]
Giguère V, McBroom LD, Flock G. Determinants of target gene specificity for ROR alpha 1: Monomeric DNA binding by an orphan nuclear receptor. Mol Cell Biol  1995; 15(5): 2517-26.
 [http://dx.doi.org/10.1128/MCB.15.5.2517] [PMID: 7739535]

[479]
Harding HP, Lazar MA. The monomer-binding orphan receptor Rev-Erb represses transcription as a dimer on a novel direct repeat. Mol Cell Biol  1995; 15(9): 4791-802.
 [http://dx.doi.org/10.1128/MCB.15.9.4791] [PMID: 7651396]

[480]
Charles JP, Shinoda T, Chinzei Y. Characterization and DNA-binding properties of GRF, a novel monomeric binding orphan receptor related to GCNF and betaFTZ-F1. Eur J Biochem  1999; 266(1): 181-90.
 [http://dx.doi.org/10.1046/j.1432-1327.1999.00842.x] [PMID: 10542063]

[481]
Paulsen RF, Granas K, Johnsen H, Rolseth V, Sterri S. Three related brain nuclear receptors, NGFI-B, Nurr1, and NOR-1, as transcriptional activators. J Mol Neurosci  1995; 6(4): 249-55.
 [http://dx.doi.org/10.1007/BF02736784] [PMID: 8860236]

[482]
Büdefeld T, Tobet SA, Majdic G. Steroidogenic factor 1 and the central nervous system. J Neuroendocrinol  2012; 24(1): 225-35.
 [http://dx.doi.org/10.1111/j.1365-2826.2011.02174.x] [PMID: 21668533]

[483]
Hattori T, Iizuka K, Horikawa Y, Takeda J. LRH-1 heterozygous knockout mice are prone to mild obesity. Endocr J  2014; 61(5): 471-80.
 [http://dx.doi.org/10.1507/endocrj.EJ14-0017] [PMID: 24531913]

[484]
Fayard E, Auwerx J, Schoonjans K. LRH-1: An orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol  2004; 14(5): 250-60.
 [http://dx.doi.org/10.1016/j.tcb.2004.03.008] [PMID: 15130581]

[485]
Dhillon H, Zigman JM, Ye C, et al. Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron  2006; 49(2): 191-203.
 [http://dx.doi.org/10.1016/j.neuron.2005.12.021] [PMID: 16423694]

[486]
Metlakunta AS, Sahu M, Yasukawa H, et al. Neuronal suppressor of cytokine signaling-3 deficiency enhances hypothalamic leptin-dependent phosphatidylinositol 3-kinase signaling. Am J Physiol Regul Integr Comp Physiol  2011; 300(5): R1185-93.
 [http://dx.doi.org/10.1152/ajpregu.00794.2010] [PMID: 21325649]

[487]
Dhillon SS, Belsham DD. Leptin differentially regulates NPY secretion in hypothalamic cell lines through distinct intracellular signal transduction pathways. Regul Pept  2011; 167(2-3): 192-200.
 [http://dx.doi.org/10.1016/j.regpep.2011.01.005] [PMID: 21262273]

[488]
Dhillon SS, McFadden SA, Chalmers JA, Centeno ML, Kim GL, Belsham DD. Cellular leptin resistance impairs the leptin-mediated suppression of neuropeptide Y secretion in hypothalamic neurons. Endocrinology  2011; 152(11): 4138-47.
 [http://dx.doi.org/10.1210/en.2011-0178] [PMID: 21914774]

[489]
Chen F, Cooney AJ, Wang Y, Law SW, O’Malley BW. Cloning of a novel orphan receptor (GCNF) expressed during germ cell development. Mol Endocrinol  1994; 8(10): 1434-44.
 [PMID: 7854358]

[490]
Sabour D, Xu X, Chung AC, et al. Germ cell nuclear factor regulates gametogenesis in developing gonads. PLoS One  2014; 9(8): e103985.
 [http://dx.doi.org/10.1371/journal.pone.0103985] [PMID: 25140725]

[491]
Cooney AJ, Hummelke GC, Herman T, Chen F, Jackson KJ. Germ cell nuclear factor is a response element-specific repressor of transcription. Biochem Biophys Res Commun  1998; 245(1): 94-100.
 [http://dx.doi.org/10.1006/bbrc.1998.8391] [PMID: 9535790]

[492]
Gu P, Le Menuet D, Chung AC, Cooney AJ. Differential recruitment of methylated CpG binding domains by the orphan receptor GCNF initiates the repression and silencing of Oct4 expression. Mol Cell Biol  2006; 26(24): 9471-83.
 [http://dx.doi.org/10.1128/MCB.00898-06] [PMID: 17030610]

[493]
Gu P, Le Menuet D, Chung AC, Cooney AJ. Differential recruitment of methylated CpG binding domains by the orphan receptor GCNF initiates the repression and silencing of Oct4 expression. Mol Cell Biol  2009; 29(7): 1987.
 [http://dx.doi.org/10.1128/MCB.00019-09] [PMID: 19279189]

[494]
Penvose A, Keenan JL, Bray D, Ramlall V, Siggers T. Comprehensive study of nuclear receptor DNA binding provides a revised framework for understanding receptor specificity. Nat Commun  2019; 10(1): 2514.
 [http://dx.doi.org/10.1038/s41467-019-10264-3] [PMID: 31175293]

[495]
Sever R, Glass CK. Signaling by nuclear receptors. Cold Spring Harb Perspect Biol  2013; 5(3): a016709.
 [http://dx.doi.org/10.1101/cshperspect.a016709] [PMID: 23457262]
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DOI https://dx.doi.org/10.2174/2772432817666220301104118	Print ISSN 2772-4328
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Current Reviews in Clinical and Experimental Pharmacology

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