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Current Drug Research Reviews

Editor-in-Chief

ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

Review Article

Phytocannabinoids as Potential Multitargeting Neuroprotectants in Alzheimer’s Disease

Author(s): Sumit S. Rathod and Yogeeta O. Agrawal*

Volume 16, Issue 2, 2024

Published on: 17 May, 2023

Page: [94 - 110] Pages: 17

DOI: 10.2174/2589977515666230502104021

Price: $65

Abstract

The Endocannabinoid System (ECS) is a well-studied system that influences a variety of physiological activities. It is evident that the ECS plays a significant role in metabolic activities and also has some neuroprotective properties. In this review, we emphasize several plant-derived cannabinoids such as β-caryophyllene (BCP), Cannabichromene (CBC), Cannabigerol (CBG), Cannabidiol (CBD), and Cannabinol (CBN), which are known to have distinctive modulation abilities of ECS. In Alzheimer's disease (AD), the activation of ECS may provide neuroprotection by modulating certain neuronal circuitry pathways through complex molecular cascades. The present article also discusses the implications of cannabinoid receptors (CB1 and CB2) as well as cannabinoid enzymes (FAAH and MAGL) modulators in AD. Specifically, CBR1 or CB2R modulations result in reduced inflammatory cytokines such as IL-2 and IL-6, as well as a reduction in microglial activation, which contribute to an inflammatory response in neurons. Furthermore, naturally occurring cannabinoid metabolic enzymes (FAAH and MAGL) inhibit the NLRP3 inflammasome complex, which may offer significant neuroprotection. In this review, we explored the multi-targeted neuroprotective properties of phytocannabinoids and their possible modulations, which could offer significant benefits in limiting AD.

Graphical Abstract

[1]
Grøntvedt GR, Schröder TN, Sando SB, White L, Bråthen G, Doeller CF. Alzheimer’s disease. Curr Biol 2018; 28(11): R645-9.
[http://dx.doi.org/10.1016/j.cub.2018.04.080] [PMID: 29870699]
[2]
Armstrong RA. What causes alzheimer’s disease? Folia Neuropathol 2013; 51(3): 169-88.
[http://dx.doi.org/10.5114/fn.2013.37702] [PMID: 24114635]
[3]
Dage JL, Wennberg AMV, Airey DC, et al. Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort. Alzheimers Dement 2016; 12(12): 1226-34.
[http://dx.doi.org/10.1016/j.jalz.2016.06.001] [PMID: 27436677]
[4]
Seeley WW, Crawford RK, Zhou J, Miller BL, Greicius MD. Neurodegenerative diseases target large-scale human brain networks. Neuron 2009; 62(1): 42-52.
[http://dx.doi.org/10.1016/j.neuron.2009.03.024] [PMID: 19376066]
[5]
Gammon K. Neurodegenerative disease: Brain windfall. Nature 2014; 515(7526): 299-300.
[http://dx.doi.org/10.1038/nj7526-299a] [PMID: 25396246]
[6]
Di Resta C, Ferrari M. New molecular approaches to Alzheimer’s disease. Clin Biochem 2019; 72: 81-6.
[http://dx.doi.org/10.1016/j.clinbiochem.2019.04.010] [PMID: 31018113]
[7]
Sala Frigerio C, Wolfs L, Fattorelli N, et al. The major risk factors for Alzheimer’s disease: Age, sex, and genes modulate the microglia response to Aβ plaques. Cell Rep 2019; 27(4): 1293-1306.e6.
[http://dx.doi.org/10.1016/j.celrep.2019.03.099] [PMID: 31018141]
[8]
Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS. Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 2005; 64(5): 834-41.
[http://dx.doi.org/10.1212/01.WNL.0000152982.47274.9E] [PMID: 15753419]
[9]
Cortés N, Andrade V, Maccioni RB. Behavioral and neuropsychiatric disorders in Alzheimer’s disease. J Alzheimers Dis 2018; 63(3): 899-910.
[http://dx.doi.org/10.3233/JAD-180005] [PMID: 29710717]
[10]
Souza RKM, Barboza AF, Gasperin G, Garcia HDBP, Barcellos PM, Nisihara R. Prevalence of dementia in patients seen at a private hospital in the Southern Region of Brazil. Einstein 2019; 18eAO4752
[http://dx.doi.org/10.31744/einstein_journal/2020AO4752] [PMID: 31664323]
[11]
Braak H, Braak E. Staging of alzheimer’s disease-related neurofibrillary changes. Neurobiol Aging 1995; 16(3): 271-8.
[http://dx.doi.org/10.1016/0197-4580(95)00021-6] [PMID: 7566337]
[12]
Villegas-Llerena C, Phillips A, Garcia-Reitboeck P, Hardy J, Pocock JM. Microglial genes regulating neuroinflammation in the progression of Alzheimer’s disease. Curr Opin Neurobiol 2016; 36: 74-81.
[http://dx.doi.org/10.1016/j.conb.2015.10.004] [PMID: 26517285]
[13]
Lu HC, Mackie K. An introduction to the endogenous cannabinoid system. Biol Psychiatry 2016; 79(7): 516-25.
[http://dx.doi.org/10.1016/j.biopsych.2015.07.028] [PMID: 26698193]
[14]
Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. Int J Mol Sci 2018; 19(3): 833.
[http://dx.doi.org/10.3390/ijms19030833] [PMID: 29533978]
[15]
Patel S, Hillard CJ. Role of endocannabinoid signaling in anxiety and depression. Curr Top Behav Neurosci 2009; 1: 347-71.
[http://dx.doi.org/10.1007/978-3-540-88955-7_14] [PMID: 21104391]
[16]
Patil AS, Mahajan UB, Agrawal YO, et al. Plant-derived natural therapeutics targeting cannabinoid receptors in metabolic syndrome and its complications: A review. Biomed Pharmacother 2020; 132110889
[http://dx.doi.org/10.1016/j.biopha.2020.110889] [PMID: 33113429]
[17]
Mouslech Z, Valla V. Endocannabinoid system: An overview of its potential in current medical practice. Neuroendocrinol Lett 2009; 30(2): 153-79.
[PMID: 19675519]
[18]
Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The plant of the thousand and one molecules. Front Plant Sci 2016; 7: 19.
[http://dx.doi.org/10.3389/fpls.2016.00019] [PMID: 26870049]
[19]
Kogan NM, Mechoulam R. Cannabinoids in health and disease. Dialogues Clin Neurosci 2007; 9(4): 413-30.
[http://dx.doi.org/10.31887/DCNS.2007.9.4/nkogan] [PMID: 18286801]
[20]
Zuardi AW, Crippa JAS, Hallak JEC, Moreira FA, Guimarães FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res 2006; 39(4): 421-9.
[http://dx.doi.org/10.1590/S0100-879X2006000400001] [PMID: 16612464]
[21]
Carroll CB, Zeissler ML, Hanemann CO, Zajicek JP. Δ9-tetrahydrocannabinol (Δ9 -THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson’s disease. Neuropathol Appl Neurobiol 2012; 38(6): 535-47.
[http://dx.doi.org/10.1111/j.1365-2990.2011.01248.x] [PMID: 22236282]
[22]
Cao C, Li Y, Liu H, et al. The potential therapeutic effects of THC on Alzheimer’s disease. J Alzheimers Dis 2014; 42(3): 973-84.
[http://dx.doi.org/10.3233/JAD-140093] [PMID: 25024327]
[23]
Gertsch J, Schoop R, Kuenzle U, Suter A. Echinacea alkylamides modulate TNF-α gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Lett 2004; 577(3): 563-9.
[http://dx.doi.org/10.1016/j.febslet.2004.10.064] [PMID: 15556647]
[24]
Raduner S, Majewska A, Chen JZ, et al. Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects. J Biol Chem 2006; 281(20): 14192-206.
[http://dx.doi.org/10.1074/jbc.M601074200] [PMID: 16547349]
[25]
Skaper SD, Facci L, Zusso M, Giusti P. An inflammation-centric view of neurological disease: Beyond the neuron. Front Cell Neurosci 2018; 12: 72.
[http://dx.doi.org/10.3389/fncel.2018.00072] [PMID: 29618972]
[26]
Kovacs GG. Concepts and classification of neurodegenerative diseases. Handb Clin Neurol 2018; 145: 301-7.
[http://dx.doi.org/10.1016/B978-0-12-802395-2.00021-3] [PMID: 28987178]
[27]
Xu S, Wang J, Jiang J, et al. TLR4 promotes microglial pyroptosis via lncRNA-F630028O10Rik by activating PI3K/AKT pathway after spinal cord injury. Cell Death Dis 2020; 11(8): 693.
[http://dx.doi.org/10.1038/s41419-020-02824-z] [PMID: 32826878]
[28]
Galal A, Slade D, Gul W, El-Alfy A, Ferreira D, Elsohly M. Naturally occurring and related synthetic cannabinoids and their potential therapeutic applications. Recent Patents CNS Drug Discov 2009; 4(2): 112-36.
[http://dx.doi.org/10.2174/157488909788453031] [PMID: 19519560]
[29]
Verrotti A, Castagnino M, Maccarrone M, Fezza F. Plant-derived and endogenous cannabinoids in epilepsy. Clin Drug Investig 2016; 36(5): 331-40.
[http://dx.doi.org/10.1007/s40261-016-0379-x] [PMID: 26892745]
[30]
Horváth B, Mukhopadhyay P, Haskó G, Pacher P. The endocannabinoid system and plant-derived cannabinoids in diabetes and diabetic complications. Am J Pathol 2012; 180(2): 432-42.
[http://dx.doi.org/10.1016/j.ajpath.2011.11.003] [PMID: 22155112]
[31]
Russo EB. Beyond Cannabis: Plants and the Endocannabinoid System. Trends Pharmacol Sci 2016; 37(7): 594-605.
[http://dx.doi.org/10.1016/j.tips.2016.04.005] [PMID: 27179600]
[32]
Sköld M, Karlberg AT, Matura M, Börje A. The fragrance chemical β-caryophyllene-air oxidation and skin sensitization. Food Chem Toxicol 2006; 44(4): 538-45.
[http://dx.doi.org/10.1016/j.fct.2005.08.028] [PMID: 16226832]
[33]
Sharma C, Al Kaabi JM, Nurulain SM, Goyal SN, Kamal MA, Ojha S. Polypharmacological properties and therapeutic potential of β-Caryophyllene: A dietary phytocannabinoid of pharmaceutical promise. Curr Pharm Des 2016; 22(21): 3237-64.
[http://dx.doi.org/10.2174/1381612822666160311115226] [PMID: 26965491]
[34]
Gertsch J, Leonti M, Raduner S, et al. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci 2008; 105(26): 9099-104.
[http://dx.doi.org/10.1073/pnas.0803601105] [PMID: 18574142]
[35]
Gertsch J. Antiinflammatory cannabinoids in diet – towards a better understanding of CB2 receptor action? Commun Integr Biol 2008; 1(1): 26-8.
[http://dx.doi.org/10.4161/cib.1.1.6568] [PMID: 19704783]
[36]
Luo M, Liu X, Zu Y, et al. Cajanol, a novel anticancer agent from Pigeonpea [Cajanus cajan (L.) Millsp. roots, induces apoptosis in human breast cancer cells through a ROS-mediated mitochondrial pathway. Chem Biol Interact 2010; 188(1): 151-60.
[http://dx.doi.org/10.1016/j.cbi.2010.07.009] [PMID: 20638373]
[37]
Hwang ES, Kim HB, Lee S, et al. Antidepressant-like effects of β-caryophyllene on restraint plus stress-induced depression. Behav Brain Res 2020; 380112439
[http://dx.doi.org/10.1016/j.bbr.2019.112439] [PMID: 31862467]
[38]
Irrera N, D’Ascola A, Pallio G, et al. β-Caryophyllene inhibits cell proliferation through a direct modulation of CB2 receptors in glioblastoma cells. Cancers 2020; 12(4): 1038.
[http://dx.doi.org/10.3390/cancers12041038] [PMID: 32340197]
[39]
Klauke AL, Racz I, Pradier B, et al. The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. Eur Neuropsychopharmacol 2014; 24(4): 608-20.
[http://dx.doi.org/10.1016/j.euroneuro.2013.10.008] [PMID: 24210682]
[40]
Aly E, Khajah MA, Masocha W. β-Caryophyllene, a CB2-Receptor-Selective phytocannabinoid, suppresses mechanical allodynia in a mouse model of antiretroviral-induced neuropathic pain. Molecules 2019; 25(1): 106.
[http://dx.doi.org/10.3390/molecules25010106] [PMID: 31892132]
[41]
Picciolo G, Pallio G, Altavilla D, et al. β-Caryophyllene reduces the inflammatory phenotype of periodontal cells by targeting CB2 receptors. Biomedicines 2020; 8(6): 164.
[http://dx.doi.org/10.3390/biomedicines8060164] [PMID: 32560286]
[42]
Koyama S, Purk A, Kaur M, et al. Beta-caryophyllene enhances wound healing through multiple routes. PLoS One 2019; 14(12)e0216104
[http://dx.doi.org/10.1371/journal.pone.0216104] [PMID: 31841509]
[43]
Chávez-Hurtado P, González-Castañeda RE, Beas-Zarate C, Flores-Soto ME, Viveros-Paredes JM. β-Caryophyllene reduces DNA oxidation and the overexpression of glial fibrillary acidic protein in the prefrontal cortex and hippocampus of d -Galactose-Induced Aged BALB/c Mice. J Med Food 2020; 23(5): 515-22.
[http://dx.doi.org/10.1089/jmf.2019.0111] [PMID: 31663807]
[44]
Lindsey LP, Daphney CM, Oppong-Damoah A, et al. The cannabinoid receptor 2 agonist, β-caryophyllene, improves working memory and reduces circulating levels of specific proinflammatory cytokines in aged male mice. Behav Brain Res 2019; 372112012
[http://dx.doi.org/10.1016/j.bbr.2019.112012] [PMID: 31173795]
[45]
Youssef DA, El-Fayoumi HM, Mahmoud MF. Beta-caryophyllene alleviates diet-induced neurobehavioral changes in rats: The role of CB2 and PPAR-γ receptors. Biomed Pharmacother 2019; 110: 145-54.
[http://dx.doi.org/10.1016/j.biopha.2018.11.039] [PMID: 30469079]
[46]
Javed H, Azimullah S, Haque ME, Ojha SK. Cannabinoid Type 2 (CB2) receptors activation protects against oxidative stress and neuroinflammation associated dopaminergic neurodegeneration in rotenone model of parkinson’s Disease. Front Neurosci 2016; 10: 321.
[http://dx.doi.org/10.3389/fnins.2016.00321] [PMID: 27531971]
[47]
Tung YT, Chua MT, Wang SY, Chang ST. Anti-inflammation activities of essential oil and its constituents from indigenous cinnamon (Cinnamomum osmophloeum) twigs. Bioresour Technol 2008; 99(9): 3908-13.
[http://dx.doi.org/10.1016/j.biortech.2007.07.050] [PMID: 17826984]
[48]
Oppong-Damoah A, Blough BE, Makriyannis A, Murnane KS. The sesquiterpene beta-caryophyllene oxide attenuates ethanol drinking and place conditioning in mice. Heliyon 2019; 5(6)e01915
[http://dx.doi.org/10.1016/j.heliyon.2019.e01915] [PMID: 31245644]
[49]
Ben Amar M. Cannabinoids in medicine: A review of their therapeutic potential. J Ethnopharmacol 2006; 105(1-2): 1-25.
[http://dx.doi.org/10.1016/j.jep.2006.02.001] [PMID: 16540272]
[50]
Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids 2010; 5(special issue): 1-21.
[51]
Kowal MA, Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2010-2014. Mult Scler 2016; 6: 1515.
[52]
Marcu JP. An overview of major and minor phytocannabinoids. Neuropathol drug Addict Subst misuse 2016; 1: 672-8.
[http://dx.doi.org/10.1016/B978-0-12-800213-1.00062-6]
[53]
Pertwee RG. The central neuropharmcology of psychotropic cannabinoids. Pharmacol Ther 1988; 36(2-3): 189-261.
[http://dx.doi.org/10.1016/0163-7258(88)90106-4] [PMID: 3279430]
[54]
Allan JD, Castillo MM, Capps KA. Stream ecology: Structure and function of running waters. Berlin: Springer 2021; pp. 1-14.
[http://dx.doi.org/10.1007/978-3-030-61286-3]
[55]
Hanuš LO, Meyer SM, Muñoz E, Taglialatela-Scafati O, Appendino G. Phytocannabinoids: A unified critical inventory. Nat Prod Rep 2016; 33(12): 1357-92.
[http://dx.doi.org/10.1039/C6NP00074F] [PMID: 27722705]
[56]
de Meijer EPM, Bagatta M, Carboni A, et al. The inheritance of chemical phenotype in Cannabis sativa L. Genetics 2003; 163(1): 335-46.
[http://dx.doi.org/10.1093/genetics/163.1.335] [PMID: 12586720]
[57]
Russo EB. Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol 2011; 163(7): 1344-64.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01238.x] [PMID: 21749363]
[58]
Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and(-)Δ9 -tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA 1998; 95(14): 8268-73.
[http://dx.doi.org/10.1073/pnas.95.14.8268] [PMID: 9653176]
[59]
Neff GW, O’Brien CB, Reddy KR, et al. Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease. Am J Gastroenterol 2002; 97(8): 2117-9.
[http://dx.doi.org/10.1111/j.1572-0241.2002.05852.x] [PMID: 12190187]
[60]
Williams SJ, Hartley JP, Graham JD. Bronchodilator effect of delta1-tetrahydrocannabinol administered by aerosol of asthmatic patients. Thorax 1976; 31(6): 720-3.
[http://dx.doi.org/10.1136/thx.31.6.720] [PMID: 797044]
[61]
Evans FJ. Cannabinoids: The separation of central from peripheral effects on a structural basis. Planta Med 1991; 57(S 1): S60-7.
[http://dx.doi.org/10.1055/s-2006-960231]
[62]
Martin BR, Compton DR, Thomas BF, et al. Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacol Biochem Behav 1991; 40(3): 471-8.
[http://dx.doi.org/10.1016/0091-3057(91)90349-7] [PMID: 1666911]
[63]
Pacher P, Mechoulam R. Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res 2011; 50(2): 193-211.
[http://dx.doi.org/10.1016/j.plipres.2011.01.001] [PMID: 21295074]
[64]
Wood CM, Pärt P. Cultured branchial epithelia from freshwater fish gills. J Exp Biol 1997; 200(6): 1047-59.
[http://dx.doi.org/10.1242/jeb.200.6.1047] [PMID: 9318858]
[65]
Upton R. Cannabis inflorescence: Cannabis spp; Standards of identity, analysis, and quality control. Scotts Valley: American Herbal Pharmacopoeia 2014.
[66]
Rhee MH, Vogel Z, Barg J, et al. Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase. J Med Chem 1997; 40(20): 3228-33.
[http://dx.doi.org/10.1021/jm970126f] [PMID: 9379442]
[67]
Appendino G, Gibbons S, Giana A, et al. Antibacterial cannabinoids from Cannabis sativa: A structure-activity study. J Nat Prod 2008; 71(8): 1427-30.
[http://dx.doi.org/10.1021/np8002673] [PMID: 18681481]
[68]
McPartland JM, Russo EB. Cannabis and cannabis extracts. J Cannabis Ther 2001; 1(3-4): 103-32.
[http://dx.doi.org/10.1300/J175v01n03_08]
[69]
Karniol IG, Shirakawa I, Takahashi RN, Knobel E, Musty RE. Effects of delta9-tetrahydrocannabinol and cannabinol in man. Pharmacology 1975; 13(6): 502-12.
[http://dx.doi.org/10.1159/000136944] [PMID: 1221432]
[70]
Turner CE, Elsohly MA, Boeren EG. Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod 1980; 43(2): 169-234.
[http://dx.doi.org/10.1021/np50008a001] [PMID: 6991645]
[71]
Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J Dermatol Sci 2007; 45(2): 87-92.
[http://dx.doi.org/10.1016/j.jdermsci.2006.10.009] [PMID: 17157480]
[72]
Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM. TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 2008; 28(24): 6231-8.
[http://dx.doi.org/10.1523/JNEUROSCI.0504-08.2008] [PMID: 18550765]
[73]
Russo EB. The pharmacological history of cannabis Handbook of Cannabis Pertwee R. Oxford, England: Oxford University Press 2014.
[http://dx.doi.org/10.1093/acprof:oso/9780199662685.003.0002]
[74]
Di Marzo V, Bisogno T, De Petrocellis L, et al. Highly selective CB(1) cannabinoid receptor ligands and novel CB(1)/VR(1) vanilloid receptor “hybrid” ligands. Biochem Biophys Res Commun 2001; 281(2): 444-51.
[http://dx.doi.org/10.1006/bbrc.2001.4354] [PMID: 11181068]
[75]
Guzmán-Venegas RA, Palma FH, Biotti PJL, de la Rosa FJB. Spectral components in electromyograms from four regions of the human masseter, in natural dentate and edentulous subjects with removable prostheses and implants. Arch Oral Biol 2018; 90: 130-7.
[http://dx.doi.org/10.1016/j.archoralbio.2018.03.010] [PMID: 29609053]
[76]
Smiley KA, Karler R, Turkanis SA. Effects of cannabinoids on the perfused rat heart. Res Commun Chem Pathol Pharmacol 1976; 14(4): 659-75.
[PMID: 959665]
[77]
Nahas G, Trouve R. Effects and interactions of natural cannabinoids on the isolated heart. Exp Biol Med 1985; 180(6): 312-2.
[http://dx.doi.org/10.3181/00379727-180-42181]
[78]
Graham JDP, Li DMF. Cardiovascular and respiratory effects of cannabis in cat and rat. Br J Pharmacol 1973; 49(1): 1-10.
[http://dx.doi.org/10.1111/j.1476-5381.1973.tb08262.x] [PMID: 4787563]
[79]
Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 2009; 1(6)a001651
[http://dx.doi.org/10.1101/cshperspect.a001651] [PMID: 20457564]
[80]
Gaoni Y, Mechoulam R. Structure+ synthesis of cannabigerol new hashish constituent. Proceedings of the Chemical Society of London. 1964; p. 82.
[81]
Grunfeld E, Gresty MA. Relationship between motion sickness, migraine and menstruation in crew members of a “round the world” yacht race. Brain Res Bull 1998; 47(5): 433-6.
[http://dx.doi.org/10.1016/S0361-9230(98)00099-9] [PMID: 10052571]
[82]
de Meijer EPM, Hammond KM, Micheler M. The inheritance of chemical phenotype in Cannabis sativa L. (III): Variation in cannabichromene proportion. Euphytica 2009; 165(2): 293-311.
[http://dx.doi.org/10.1007/s10681-008-9787-1]
[83]
Gauson LA, Stevenson LA, Thomas A, Baillie GL, Ross RA, Pertwee RG. Cannabigerol behaves as a partial agonist at both CB1 and CB2 receptors. Proceedings 17th Annual Symposium on the Cannabinoids International Cannabinoid Research Society. Saint-Sauveur, QC. 2007; p. 206.
[84]
Cascio MG, Gauson LA, Stevenson LA, Ross RA, Pertwee RG. Evidence that the plant cannabinoid cannabigerol is a highly potent α2-adrenoceptor agonist and moderately potent 5HT1A receptor antagonist. Br J Pharmacol 2010; 159(1): 129-41.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00515.x] [PMID: 20002104]
[85]
De Petrocellis L, Di Marzo V. Non-CB1, non-CB2 receptors for endocannabinoids, plant cannabinoids, and synthetic cannabimimetics: Focus on G-protein-coupled receptors and transient receptor potential channels. J Neuroimmune Pharmacol 2010; 5(1): 103-21.
[http://dx.doi.org/10.1007/s11481-009-9177-z] [PMID: 19847654]
[86]
Banerjee SP, Snyder SH, Mechoulam R. Cannabinoids: Influence on neurotransmitter uptake in rat brain synaptosomes. J Pharmacol Exp Ther 1975; 194(1): 74-81.
[PMID: 168349]
[87]
Gugliandolo A, Pollastro F, Grassi G, Bramanti P, Mazzon E. In Vitro Model of neuroinflammation: Efficacy of Cannabigerol, a non-psychoactive Cannabinoid. Int J Mol Sci 2018; 19(7): 1992.
[http://dx.doi.org/10.3390/ijms19071992] [PMID: 29986533]
[88]
Navarro G, Morales P, Rodríguez-Cueto C, Fernández-Ruiz J, Jagerovic N, Franco R. Targeting cannabinoid CB2 receptors in the central nervous system. Medicinal chemistry approaches with focus on neurodegenerative disorders. Front Neurosci 2016; 10: 406.
[http://dx.doi.org/10.3389/fnins.2016.00406] [PMID: 27679556]
[89]
Sghendo L, Mifsud J. Understanding the molecular pharmacology of the serotonergic system:Using fluoxetine as a model. J Pharm Pharmacol 2012; 64(3): 317-25.
[http://dx.doi.org/10.1111/j.2042-7158.2011.01384.x] [PMID: 22309263]
[90]
Claussen U, Von Spulak F, Korte F. Chemical classification of plants. XXXI. Hashish. 10. Cannabichromene, a new hashish component. Tetrahedron 1966; 22(4): 1477-9.
[http://dx.doi.org/10.1016/S0040-4020(01)99445-1]
[91]
De Meijer E. Cannabis sativa plants rich in cannabichromene and its acid, extracts thereof and methods of obtaining extracts therefrom. In: US20160360721A1, 2011.
[92]
Mehmedic Z, Chandra S, Slade D, et al. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci 2010; 55(5): 1209-17.
[http://dx.doi.org/10.1111/j.1556-4029.2010.01441.x] [PMID: 20487147]
[93]
Swift W, Wong A, Li KM, Arnold JC, McGregor IS. Analysis of cannabis seizures in NSW, Australia: Cannabis potency and cannabinoid profile. PLoS One 2013; 8(7)e70052
[http://dx.doi.org/10.1371/journal.pone.0070052] [PMID: 23894589]
[94]
Iwata N, Kitanaka S. New cannabinoid-like chromane and chromene derivatives from Rhododendron anthopogonoides. Chem Pharm Bull 2011; 59(11): 1409-12.
[http://dx.doi.org/10.1248/cpb.59.1409] [PMID: 22041081]
[95]
Udoh M, Santiago M, Devenish S, McGregor IS, Connor M. Cannabichromene is a cannabinoid CB 2 receptor agonist. Br J Pharmacol 2019; 176(23): 4537-47.
[http://dx.doi.org/10.1111/bph.14815] [PMID: 31368508]
[96]
O’Neil JD, Dalton WS, Forney RB. The effect of cannabichromene on mean blood pressure, heart rate, and respiration rate responses to tetrahydrocannabinol in the anesthetized rat. Toxicol Appl Pharmacol 1979; 49(2): 265-70.
[http://dx.doi.org/10.1016/0041-008X(79)90250-3] [PMID: 494278]
[97]
Grueter BA, Brasnjo G, Malenka RC. Postsynaptic TRPV1 triggers cell type–specific long-term depression in the nucleus accumbens. Nat Neurosci 2010; 13(12): 1519-25.
[http://dx.doi.org/10.1038/nn.2685] [PMID: 21076424]
[98]
Lerner TN, Kreitzer AC. RGS4 is required for dopaminergic control of striatal LTD and susceptibility to parkinsonian motor deficits. Neuron 2012; 73(2): 347-59.
[http://dx.doi.org/10.1016/j.neuron.2011.11.015] [PMID: 22284188]
[99]
Chávez AE, Chiu CQ, Castillo PE. TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat Neurosci 2010; 13(12): 1511-8.
[http://dx.doi.org/10.1038/nn.2684] [PMID: 21076423]
[100]
Dhopeshwarkar A, Mackie K. CB2 Cannabinoid receptors as a therapeutic target-what does the future hold? Mol Pharmacol 2014; 86(4): 430-7.
[http://dx.doi.org/10.1124/mol.114.094649] [PMID: 25106425]
[101]
Atwood BK, Mackie K. CB2: A cannabinoid receptor with an identity crisis. Br J Pharmacol 2010; 160(3): 467-79.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00729.x] [PMID: 20590558]
[102]
Gong JP, Onaivi ES, Ishiguro H, et al. Cannabinoid CB2 receptors: Immunohistochemical localization in rat brain. Brain Res 2006; 1071(1): 10-23.
[http://dx.doi.org/10.1016/j.brainres.2005.11.035] [PMID: 16472786]
[103]
den Boon FS, Chameau P, Schaafsma-Zhao Q, et al. Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors. Proc Natl Acad Sci 2012; 109(9): 3534-9.
[http://dx.doi.org/10.1073/pnas.1118167109] [PMID: 22331871]
[104]
Min R, Di Marzo V, Mansvelder HD. DAG lipase involvement in depolarization-induced suppression of inhibition: Does endocannabinoid biosynthesis always meet the demand? Neuroscientist 2010; 16(6): 608-13.
[http://dx.doi.org/10.1177/1073858410373281]
[105]
Katona I, Sperlágh B, Sík A, et al. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 1999; 19(11): 4544-58.
[http://dx.doi.org/10.1523/JNEUROSCI.19-11-04544.1999] [PMID: 10341254]
[106]
Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol 2005; 168(168): 299-325.
[http://dx.doi.org/10.1007/3-540-26573-2_10] [PMID: 16596779]
[107]
Tsou K, Brown S, Sañudo-Peña MC, Mackie K, Walker JM. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 1998; 83(2): 393-411.
[http://dx.doi.org/10.1016/S0306-4522(97)00436-3] [PMID: 9460749]
[108]
Maroso M, Szabo GG, Kim HK, et al. Cannabinoid control of learning and memory through HCN channels. Neuron 2016; 89(5): 1059-73.
[http://dx.doi.org/10.1016/j.neuron.2016.01.023] [PMID: 26898775]
[109]
Maccarrone M, Bab I, Bíró T, et al. Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci 2015; 36(5): 277-96.
[http://dx.doi.org/10.1016/j.tips.2015.02.008] [PMID: 25796370]
[110]
Tam J, Trembovler V, Di Marzo V, et al. The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J 2008; 22(1): 285-94.
[http://dx.doi.org/10.1096/fj.06-7957com] [PMID: 17704191]
[111]
Clapper JR, Moreno-Sanz G, Russo R, et al. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nat Neurosci 2010; 13(10): 1265-70.
[http://dx.doi.org/10.1038/nn.2632] [PMID: 20852626]
[112]
Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346(6284): 561-4.
[http://dx.doi.org/10.1038/346561a0] [PMID: 2165569]
[113]
Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365(6441): 61-5.
[http://dx.doi.org/10.1038/365061a0] [PMID: 7689702]
[114]
Lange JHM, Coolen HKAC, van Stuivenberg HH, et al. Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB(1) cannabinoid receptor antagonists. J Med Chem 2004; 47(3): 627-43.
[http://dx.doi.org/10.1021/jm031019q] [PMID: 14736243]
[115]
Lange JHM, Sanders HJ, van Rheenen J. An expedient atom-efficient synthesis of the cannabinoid CB1 receptor inverse agonist ibipinabant. Tetrahedron Lett 2011; 52(12): 1303-5.
[http://dx.doi.org/10.1016/j.tetlet.2011.01.068]
[116]
Kim M, Yun H, Kwak H, Kim J, Lee J. Design, chemical synthesis, and biological evaluation of novel triazolyl analogues of taranabant (MK-0364), a cannabinoid-1 receptor inverse agonist. Tetrahedron 2008; 64(48): 10802-9.
[http://dx.doi.org/10.1016/j.tet.2008.09.057]
[117]
Woods SC. The endocannabinoid system:Novel pathway for cardiometabolic risk-factor reduction. JAAPA 2007; 7-10.
[118]
Tang J, Chen Q, Guo J, et al. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by activating cannabinoid receptor 2. Mol Neurobiol 2016; 53(3): 1935-48.
[http://dx.doi.org/10.1007/s12035-015-9154-x] [PMID: 25833102]
[119]
Kofman O, van Embden S, Alpert C, Fuchs I. Central and peripheral minocycline suppresses motor activity in rats. Pharmacol Biochem Behav 1993; 44(2): 397-402.
[http://dx.doi.org/10.1016/0091-3057(93)90481-8] [PMID: 8383342]
[120]
Darlington CL. Dexanabinol: A novel cannabinoid with neuroprotective properties. IDrugs 2003; 6(10): 976.
[121]
Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K. Withdrawal phenomena and dependence syndrome after the consumption of “spice gold”. Dtsch Arztebl Int 2009; 106(27): 464-7.
[http://dx.doi.org/10.3238/arztebl.2009.0464] [PMID: 19652769]
[122]
Atwood BK, Huffman J, Straiker A, Mackie K. JWH018, a common constituent of ‘Spice’ herbal blends, is a potent and efficacious cannabinoid CB 1 receptor agonist. Br J Pharmacol 2010; 160(3): 585-93.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00582.x] [PMID: 20100276]
[123]
Schlosburg JE, Blankman JL, Long JZ, et al. Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci 2010; 13(9): 1113-9.
[http://dx.doi.org/10.1038/nn.2616] [PMID: 20729846]
[124]
Marinelli S, Pacioni S, Bisogno T, et al. The endocannabinoid 2-arachidonoylglycerol is responsible for the slow self-inhibition in neocortical interneurons. J Neurosci 2008; 28(50): 13532-41.
[http://dx.doi.org/10.1523/JNEUROSCI.0847-08.2008] [PMID: 19074027]
[125]
Bacci A, Huguenard JR, Prince DA. Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 2004; 431(7006): 312-6.
[http://dx.doi.org/10.1038/nature02913] [PMID: 15372034]
[126]
Turu G, Hunyady L. Signal transduction of the CB1 cannabinoid receptor. J Mol Endocrinol 2010; 44(2): 75-85.
[http://dx.doi.org/10.1677/JME-08-0190] [PMID: 19620237]
[127]
Bai Y, Li Z, Liu W, Gao D, Liu M, Zhang P. Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway. Acta Cir Bras 2019; 34(11)e201901104
[http://dx.doi.org/10.1590/s0102-865020190110000004] [PMID: 31859817]
[128]
Guo M, Lu H, Qin J, et al. Biochanin a provides neuroprotection against Cerebral Ischemia/Reperfusion injury by Nrf2-Mediated Inhibition of oxidative stress and inflammation signaling pathway in rats. Med Sci Monit 2019; 25: 8975-83.
[http://dx.doi.org/10.12659/MSM.918665] [PMID: 31767824]
[129]
Thors L, Eriksson J, Fowler CJ. Inhibition of the cellular uptake of anandamide by genistein and its analogue daidzein in cells with different levels of fatty acid amide hydrolase-driven uptake. Br J Pharmacol 2007; 152(5): 744-50.
[http://dx.doi.org/10.1038/sj.bjp.0707401] [PMID: 17676056]
[130]
Yang R, Lu Y, Liu J. Identification of tanshinone IIA as a natural monoacylglycerol lipase inhibitor by combined in silico and in vitro approach. MedChemComm 2014; 5(10): 1528-32.
[http://dx.doi.org/10.1039/C4MD00186A]
[131]
Wang Z, Yang X, Zhang W, Zhang P, Jiang B. Tanshinone IIA attenuates nerve structural and functional damage induced by nerve crush injury in rats. PLoS One 2018; 13(8)e0202532
[http://dx.doi.org/10.1371/journal.pone.0202532] [PMID: 30138344]
[132]
Wang H, Zhong L, Mi S, Song N, Zhang W, Zhong M. Tanshinone IIA prevents platelet activation and down-regulates CD36 and MKK4/JNK2 signaling pathway. BMC Cardiovasc Disord 2020; 20(1): 81.
[http://dx.doi.org/10.1186/s12872-019-01289-z] [PMID: 32059638]
[133]
Scalvini L, Piomelli D, Mor M. Monoglyceride lipase: Structure and inhibitors. Chem Phys Lipids 2016; 197: 13-24.
[http://dx.doi.org/10.1016/j.chemphyslip.2015.07.011] [PMID: 26216043]
[134]
Costola-de-Souza C, Ribeiro A, Ferraz-de-Paula V, Pinheiro ML, Palermo-Neto J. 50. Inhibitors of monoacylglycerol lipase, URB602 and JZL184, decrease inflammation in a dose-dependent murine model of acute lung injury. Brain Behav Immun 2012; 26: S14.
[http://dx.doi.org/10.1016/j.bbi.2012.07.074]
[135]
Kwon HS, Koh SH. Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes. Transl Neurodegener 2020; 9(1): 42.
[http://dx.doi.org/10.1186/s40035-020-00221-2] [PMID: 33239064]
[136]
Muzio L, Viotti A, Martino G. Microglia in Neuroinflammation and Neurodegeneration: From understanding to therapy. Front Neurosci 2021; 15742065
[137]
Kempuraj D, Thangavel R, Natteru PA, Selvakumar GP, Saeed D, Zahoor H, et al. Neuroinflammation induces Neurodegeneration. J Neurol Neurosurg spine 2016; 1(1)
[138]
Twitchell W, Brown S, Mackie K. Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J Neurophysiol 1997; 78(1): 43-50.
[http://dx.doi.org/10.1152/jn.1997.78.1.43] [PMID: 9242259]
[139]
Swerdlow RH. Pathogenesis of Alzheimer’s disease. Clin Interv Aging 2007; 2(3): 347-59.
[PMID: 18044185]
[140]
Duyckaerts C, Dickson D. Neuropathology of Alzheimer’s disease and its variants Neurodegener Mol Pathol Dement Mov Disord. Wiley Online Library 2011; p. 62.
[141]
Fonnum F. Glutamate: A neurotransmitter in mammalian brain. J Neurochem 1984; 42(1): 1-11.
[http://dx.doi.org/10.1111/j.1471-4159.1984.tb09689.x] [PMID: 6139418]
[142]
Willard SS, Koochekpour S. Glutamate, glutamate receptors, and downstream signaling pathways. Int J Biol Sci 2013; 9(9): 948-59.
[http://dx.doi.org/10.7150/ijbs.6426] [PMID: 24155668]
[143]
Riedel G, Platt B, Micheau J. Glutamate receptor function in learning and memory. Behav Brain Res 2003; 140(1-2): 1-47.
[http://dx.doi.org/10.1016/S0166-4328(02)00272-3] [PMID: 12644276]
[144]
Lewerenz J, Maher P. Chronic glutamate toxicity in neurodegenerative diseases-what is the evidence? Front Neurosci 2015; 9: 469.
[http://dx.doi.org/10.3389/fnins.2015.00469] [PMID: 26733784]
[145]
Ragnarsson L, Dodd PR, Hynd MR. Role of ionotropic glutamate receptors in neurodegenerative and other disorders Handbook of neurotoxicity. New York: Springer 2014; pp. 1039-70.
[http://dx.doi.org/10.1007/978-1-4614-5836-4_144]
[146]
Bagley KC, Abdelwahab SF, Tuskan RG, Lewis GK. Calcium signaling through phospholipase C activates dendritic cells to mature and is necessary for the activation and maturation of dendritic cells induced by diverse agonists. Clin Diagn Lab Immunol 2004; 11(1): 77-82.
[PMID: 14715548]
[147]
Zhang J, Wang X, Vikash V, et al. ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev 2016; 2016: 1-18.
[http://dx.doi.org/10.1155/2016/4350965] [PMID: 26998193]
[148]
Salter MW, Stevens B. Microglia emerge as central players in brain disease. Nat Med 2017; 23(9): 1018-27.
[http://dx.doi.org/10.1038/nm.4397] [PMID: 28886007]
[149]
Bachiller S, Jiménez-Ferrer I, Paulus A, Yang Y, Swanberg M, Deierborg T, et al. Microglia in Neurological diseases: A road map to brain-disease dependent-inflammatory response. Front Cell Neurosci 2018; 12: 488.
[150]
Harry GJ, Kraft AD. Neuroinflammation and microglia: Considerations and approaches for neurotoxicity assessment. Expert Opin Drug Metab Toxicol 2008; 4(10): 1265-77.
[http://dx.doi.org/10.1517/17425255.4.10.1265] [PMID: 18798697]
[151]
Deming Y, Li Z, Benitez BA, Cruchaga C. Triggering receptor expressed on myeloid cells 2 (TREM2): A potential therapeutic target for Alzheimer disease? Expert Opin Ther Targets 2018; 22(7): 587-98.
[http://dx.doi.org/10.1080/14728222.2018.1486823] [PMID: 29889572]
[152]
McQuade A, Kang YJ, Hasselmann J, et al. Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer’s disease. Nat Commun 2020; 11(1): 5370.
[http://dx.doi.org/10.1038/s41467-020-19227-5] [PMID: 33097708]
[153]
Chen CY, Shih YC, Hung YF, Hsueh YP. Beyond defense: Regulation of neuronal morphogenesis and brain functions via Toll-like receptors. J Biomed Sci 2019; 26(1): 90.
[http://dx.doi.org/10.1186/s12929-019-0584-z] [PMID: 31684953]
[154]
Huang H, Nguyen PT, Schwab NA, Tanner JJ, Price CC, Ding M. Mapping dorsal and ventral caudate in older adults: Method and validation. Front Aging Neurosci 2017; 9: 91.
[http://dx.doi.org/10.3389/fnagi.2017.00091] [PMID: 28420985]
[155]
Richard KL, Filali M, Préfontaine P, Rivest S. Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid β 1-42 and delay the cognitive decline in a mouse model of Alzheimer’s disease. J Neurosci 2008; 28(22): 5784-93.
[http://dx.doi.org/10.1523/JNEUROSCI.1146-08.2008] [PMID: 18509040]
[156]
Jana M, Palencia CA, Pahan K. Fibrillar amyloid-β peptides activate microglia via TLR2: Implications for Alzheimer’s disease. J Immunol 2008; 181(10): 7254-62.
[http://dx.doi.org/10.4049/jimmunol.181.10.7254] [PMID: 18981147]
[157]
Smith SMC, Friedle SA, Watters JJ. Chronic intermittent hypoxia exerts CNS region-specific effects on rat microglial inflammatory and TLR4 gene expression. PLoS One 2013; 8(12)e81584
[http://dx.doi.org/10.1371/journal.pone.0081584] [PMID: 24324707]
[158]
Wang F-X, Liu S-Y, Zheng X, Chen X, Lu L-X, Chen B, et al. TLR1 expression in mouse brain was increased in a KA-induced seizure model. Inflamm Res 2015; 64(7): 487-95.
[159]
Hu QP, Mao DA. Histone deacetylase inhibitor SAHA attenuates post-seizure hippocampal microglia TLR4/MYD88 signaling and inhibits TLR4 gene expression via histone acetylation. BMC Neurosci 2016; 17(1): 22.
[http://dx.doi.org/10.1186/s12868-016-0264-9] [PMID: 27193049]
[160]
Béraud D, Twomey M, Bloom B, et al. α-Synuclein alters toll-like receptor expression. Front Neurosci 2011; 5: 80.
[http://dx.doi.org/10.3389/fnins.2011.00080] [PMID: 21747756]
[161]
Milly PCD, Dunne KA. Colorado river flow dwindles as warming-driven loss of reflective snow energizes evaporation. Science 2020; 567: 6483.
[http://dx.doi.org/10.1126/science.aay9187]
[162]
Iliev AI, Stringaris AK, Nau R, Neumann H. Neuronal injury mediated via stimulation of microglial toll-like receptor-9 (TLR9). FASEB J 2004; 18(2): 1-17.
[http://dx.doi.org/10.1096/fj.03-0670fje] [PMID: 14688201]
[163]
Qin Y, Liu Y, Hao W, et al. Stimulation of TLR4 attenuates Alzheimer’s disease–related symptoms and pathology in tau-transgenic mice. J Immunol 2016; 197(8): 3281-92.
[http://dx.doi.org/10.4049/jimmunol.1600873] [PMID: 27605009]
[164]
Takeda K, Akira S. TLR signaling pathways. Semin Immunol 2004; 16(1): 3-9.
[http://dx.doi.org/10.1016/j.smim.2003.10.003] [PMID: 14751757]
[165]
Zhang FX, Kirschning CJ, Mancinelli R, et al. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem 1999; 274(12): 7611-4.
[http://dx.doi.org/10.1074/jbc.274.12.7611] [PMID: 10075645]
[166]
Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2(10)a006296
[http://dx.doi.org/10.1101/cshperspect.a006296] [PMID: 23028126]
[167]
Sharma C, Kim S, Nam Y, Jung UJ, Kim SR. Mitochondrial dysfunction as a driver of cognitive impairment in Alzheimer’s disease. Int J Mol Sci 2021; 22(9): 4850.
[http://dx.doi.org/10.3390/ijms22094850] [PMID: 34063708]
[168]
Swerdlow RH. Mitochondria and Mitochondrial Cascades in Alzheimer’s disease. J Alzheimers Dis 2018; 62(3): 1403-16.
[http://dx.doi.org/10.3233/JAD-170585] [PMID: 29036828]
[169]
Swerdlow RH, Burns JM, Khan SM. The Alzheimer’s disease mitochondrial cascade hypothesis: Progress and perspectives. Biochim Biophys Acta 2014; 1842(8): 1219-31.
[170]
Coskun PE, Wyrembak J, Derbereva O, Melkonian G, Doran E, Lott IT, et al. Systemic mitochondrial dysfunction and the etiology of Alzheimer’s disease and down syndrome dementia. Biochim Biophys Acta 2014; 1842(8): 1219-31.
[171]
Chen JX, Yan SD. Amyloid-beta-induced mitochondrial dysfunction. J Alzheimers Dis 2010; 20(S 2): S293-310.
[http://dx.doi.org/10.3233/JAD-2007-12208] [PMID: 17917162]
[172]
Flannery PJ, Trushina E. Mitochondrial dynamics and transport in Alzheimer’s disease. Mol Cell Neurosci 2019; 98: 109-20.
[http://dx.doi.org/10.1016/j.mcn.2019.06.009] [PMID: 31216425]
[173]
Newman LE, Shadel GS. Pink1/Parkin link inflammation, mitochondrial stress, and neurodegeneration. J Cell Biol 2018; 217(10): 3327-9.
[http://dx.doi.org/10.1083/jcb.201808118] [PMID: 30154188]
[174]
Buée L, Bussière T, Buée-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders11These authors contributed equally to this work. Brain Res Brain Res Rev 2000; 33(1): 95-130.
[http://dx.doi.org/10.1016/S0165-0173(00)00019-9] [PMID: 10967355]
[175]
Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82(4): 239-59.
[http://dx.doi.org/10.1007/BF00308809] [PMID: 1759558]
[176]
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 2002; 297(5580): 353-6.
[http://dx.doi.org/10.1126/science.1072994]
[177]
Bliss TVP, Collingridge GL. A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 1993; 361(6407): 31-9.
[http://dx.doi.org/10.1038/361031a0] [PMID: 8421494]
[178]
Honer WG, Dickson DW, Gleeson J, Davies P. Regional synaptic pathology in Alzheimer’s disease. Neurobiol Aging 1992; 13(3): 375-82.
[http://dx.doi.org/10.1016/0197-4580(92)90111-A] [PMID: 1625766]
[179]
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]
[180]
Selkoe DJ. Alzheimer’s disease is a synaptic failure. Science 2002; 298(5594): 789-91.
[http://dx.doi.org/10.1126/science.1074069]
[181]
Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in alzheimer’s disease: Synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991; 30(4): 572-80.
[http://dx.doi.org/10.1002/ana.410300410] [PMID: 1789684]
[182]
Davies CA, Mann DMA, Sumpter PQ, Yates PO. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer’s disease. J Neurol Sci 1987; 78(2): 151-64.
[http://dx.doi.org/10.1016/0022-510X(87)90057-8] [PMID: 3572454]
[183]
Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology 2007; 68(18): 1501-8.
[http://dx.doi.org/10.1212/01.wnl.0000260698.46517.8f] [PMID: 17470753]
[184]
Scheff SW, Price DA. Alzheimer’s disease-related synapse loss in the cingulate cortex. J Alzheimers Dis 2001; 3(5): 495-505.
[http://dx.doi.org/10.3233/JAD-2001-3509] [PMID: 12214036]
[185]
Noble W, Hanger DP, Miller CCJ, Lovestone S. The importance of tau phosphorylation for neurodegenerative diseases. Front Neurol 2013; 4: 83.
[http://dx.doi.org/10.3389/fneur.2013.00083] [PMID: 23847585]
[186]
Wang X, Destrument A, Tournier C. Physiological roles of MKK4 and MKK7: Insights from animal models. Biochim Biophys Acta Mol Cell Res 2007; 1773(8): 1349-57.
[http://dx.doi.org/10.1016/j.bbamcr.2006.10.016] [PMID: 17157936]
[187]
Han Z, Boyle DL, Chang L, et al. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J Clin Invest 2001; 108(1): 73-81.
[http://dx.doi.org/10.1172/JCI12466] [PMID: 11435459]
[188]
Schepetkin IA, Kirpotina LN, Hammaker D, et al. Anti-inflammatory effects and joint protection in collagen-induced arthritis after treatment with iq-1s, a selective c-jun n-terminal kinase inhibitor. J Pharmacol Exp Ther 2015; 353(3): 505-16.
[http://dx.doi.org/10.1124/jpet.114.220251] [PMID: 25784649]
[189]
Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ. Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH 2 -terminal kinase. Proc Natl Acad Sci USA 1997; 94(14): 7337-42.
[http://dx.doi.org/10.1073/pnas.94.14.7337] [PMID: 9207092]
[190]
Zhang C, Yang Y, Gao Y, Sun D. NaF-induced neurotoxicity via activation of the IL-1β/JNK signaling pathway. Toxicology 2022; 469153132
[http://dx.doi.org/10.1016/j.tox.2022.153132] [PMID: 35172196]
[191]
Asih PR, Prikas E, Stefanoska K, Tan ARP, Ahel HI, Ittner A. Functions of p38 MAP kinases in the central nervous system. Front Mol Neurosci 2020; 13570586
[http://dx.doi.org/10.3389/fnmol.2020.570586] [PMID: 33013322]
[192]
Li Y, Xu X, Wang L, et al. REDD1 (regulated in development and DNA damage-1)/autophagy inhibition ameliorates fine particulate matter (PM2.5) -induced inflammation and apoptosis in BEAS-2B cells. Bioengineered 2021; 12(1): 1403-14.
[http://dx.doi.org/10.1080/21655979.2021.1917227] [PMID: 33926343]
[193]
Miller WP, Sunilkumar S, Dennis MD. The stress response protein REDD1 as a causal factor for oxidative stress in diabetic retinopathy. Free Radic Biol Med 2021; 165: 127-36.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.01.041] [PMID: 33524531]
[194]
Maiese K, Chong ZZ, Shang YC, Wang S. mTOR: On target for novel therapeutic strategies in the nervous system. Trends Mol Med 2013; 19(1): 51-60.
[http://dx.doi.org/10.1016/j.molmed.2012.11.001] [PMID: 23265840]
[195]
Kany S, Vollrath JT, Relja B. Cytokines in Inflammatory Disease. Int J Mol Sci 2019; 20(23): 6008.
[http://dx.doi.org/10.3390/ijms20236008] [PMID: 31795299]
[196]
Yan W, Dong H, Xiong L. The protective roles of autophagy in ischemic preconditioning. Acta Pharmacol Sin 2013; 34(5): 636-43.
[http://dx.doi.org/10.1038/aps.2013.18] [PMID: 23603984]
[197]
Hampel H, Caraci F, Cuello AC, et al. A path toward precision medicine for neuroinflammatory mechanisms in Alzheimer’s disease. Front Immunol 2020; 11: 456.
[http://dx.doi.org/10.3389/fimmu.2020.00456] [PMID: 32296418]
[198]
Fernández-Ruiz J, Moreno-Martet M, Rodríguez-Cueto C, et al. Prospects for cannabinoid therapies in basal ganglia disorders. Br J Pharmacol 2011; 163(7): 1365-78.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01365.x] [PMID: 21545415]
[199]
Bilkei-Gorzo A. The endocannabinoid system in normal and pathological brain ageing. Philos Trans R Soc Lond B Biol Sci 2012; 367(1607): 3326-41.
[http://dx.doi.org/10.1098/rstb.2011.0388] [PMID: 23108550]
[200]
Scotter EL, Abood ME, Glass M. The endocannabinoid system as a target for the treatment of neurodegenerative disease. Br J Pharmacol 2010; 160(3): 480-98.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00735.x] [PMID: 20590559]
[201]
Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC. Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. J Neurosci 1991; 11(2): 563-83.
[http://dx.doi.org/10.1523/JNEUROSCI.11-02-00563.1991] [PMID: 1992016]
[202]
Marsicano G, Kuner R. Anatomical distribution of receptors, ligands and enzymes in the brain and in the spinal cord: Circuitries and neurochemistryCannabinoids and the Brain. Springer 2008; pp. 161-201.
[http://dx.doi.org/10.1007/978-0-387-74349-3_10]
[203]
Straiker A, Mackie K. Depolarization-induced suppression of excitation in murine autaptic hippocampal neurones. J Physiol 2005; 569(2): 501-17.
[http://dx.doi.org/10.1113/jphysiol.2005.091918] [PMID: 16179366]
[204]
Klein TW. Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol 2005; 5(5): 400-11.
[http://dx.doi.org/10.1038/nri1602] [PMID: 15864274]
[205]
Mackie K. Mechanisms of CB1 receptor signaling: Endocannabinoid modulation of synaptic strength. Int J Obes 2006; 30(S1) (Suppl. 1): S19-23.
[http://dx.doi.org/10.1038/sj.ijo.0803273] [PMID: 16570100]
[206]
Palazuelos J, Aguado T, Pazos MR, et al. Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain 2009; 132(11): 3152-64.
[http://dx.doi.org/10.1093/brain/awp239] [PMID: 19805493]
[207]
Seth AK, Barrett AB, Barnett L. Granger causality analysis in neuroscience and neuroimaging. J Neurosci 2015; 35(8): 3293-7.
[http://dx.doi.org/10.1523/JNEUROSCI.4399-14.2015] [PMID: 25716830]
[208]
Sagredo O, García-Arencibia M, de Lago E, Finetti S, Decio A, Fernández-Ruiz J. Cannabinoids and neuroprotection in basal ganglia disorders. Mol Neurobiol 2007; 36(1): 82-91.
[http://dx.doi.org/10.1007/s12035-007-0004-3] [PMID: 17952653]
[209]
Grayson DS, Bliss-Moreau E, Machado CJ, et al. The rhesus monkey connectome predicts disrupted functional networks resulting from pharmacogenetic inactivation of the amygdala. Neuron 2016; 91(2): 453-66.
[http://dx.doi.org/10.1016/j.neuron.2016.06.005] [PMID: 27477019]
[210]
Swami M. Brain cannabinoid CB2 receptors modulate cocaine’s actions in mice. Nat Med 2011; 17(9): 1059.
[http://dx.doi.org/10.1038/nm.2483]
[211]
Singla S, Sachdeva R, Mehta JL. Cannabinoids and atherosclerotic coronary heart disease. Clin Cardiol 2012; 35(6): 329-35.
[http://dx.doi.org/10.1002/clc.21962] [PMID: 22278660]
[212]
Brierley DI, Samuels J, Duncan M, Whalley BJ, Williams CM. Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats. Psychopharmacology 2016; 233(19-20): 3603-13.
[http://dx.doi.org/10.1007/s00213-016-4397-4] [PMID: 27503475]
[213]
Izzo AA, Capasso R, Aviello G, et al. Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammation-induced hypermotility in mice. Br J Pharmacol 2012; 166(4): 1444-60.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01879.x] [PMID: 22300105]
[214]
Thors L, Burston JJ, Alter BJ, et al. Biochanin A, a naturally occurring inhibitor of fatty acid amide hydrolase. Br J Pharmacol 2010; 160(3): 549-60.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00716.x] [PMID: 20590565]
[215]
Stone NL, Murphy AJ, England TJ, O’Sullivan SE. A systematic review of minor phytocannabinoids with promising neuroprotective potential. Br J Pharmacol 2020; 177(19 bph.): 15185.
[http://dx.doi.org/10.1111/bph.15185] [PMID: 32608035]
[216]
Mechoulam R, Lander N, University A, Zahalka J. Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative. Tetrahedron Asymmetry 1990; 1(5): 315-8.
[http://dx.doi.org/10.1016/S0957-4166(00)86322-3]
[217]
Fong TM, Heymsfield SB. Cannabinoid-1 receptor inverse agonists: Current understanding of mechanism of action and unanswered questions. Int J Obes 2009; 33(9): 947-55.
[http://dx.doi.org/10.1038/ijo.2009.132] [PMID: 19597516]
[218]
Kiessling LL, Strong LE, Gestwicki JE. Annual Reports in Medicinal Chemistry. San Diego, CA: Academic Press Inc. 2000.

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