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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection

Author(s): Federico López Couselo, Julieta Saba, Lila Carniglia, Daniela Durand, Mercedes Lasaga and Carla Caruso*

Volume 23, Issue 9, 2024

Published on: 24 October, 2023

Page: [1101 - 1119] Pages: 19

DOI: 10.2174/0118715273269881231012062255

Price: $65

Abstract

Astrocytes are glial cells that perform several fundamental physiological functions within the brain. They can control neuronal activity and levels of ions and neurotransmitters, and release several factors that modulate the brain environment. Over the past few decades, our knowledge of astrocytes and their functions has rapidly evolved. Neurodegenerative diseases are characterized by selective degeneration of neurons, increased glial activation, and glial dysfunction. Given the significant role played by astrocytes, there is growing interest in their potential therapeutic role. However, defining their contribution to neurodegeneration is more complex than was previously thought. This review summarizes the main functions of astrocytes and their involvement in neurodegenerative diseases, highlighting their neurotoxic and neuroprotective ability.

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[1]
von Bartheld CS, Bahney J, Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting. J Comp Neurol 2016; 524(18): 3865-95.
[http://dx.doi.org/10.1002/cne.24040] [PMID: 27187682]
[2]
Sofroniew MV, Vinters HV. Astrocytes: Biology and pathology. Acta Neuropathol 2010; 119(1): 7-35.
[http://dx.doi.org/10.1007/s00401-009-0619-8] [PMID: 20012068]
[3]
Oberheim NA, Goldman SA, Nedergaard M. Heterogeneity of astrocytic form and function. Methods Mol Biol 2012; 814: 23-45.
[http://dx.doi.org/10.1007/978-1-61779-452-0_3] [PMID: 22144298]
[4]
Oberheim NA, Takano T, Han X, et al. Uniquely hominid features of adult human astrocytes. J Neurosci 2009; 29(10): 3276-87.
[http://dx.doi.org/10.1523/JNEUROSCI.4707-08.2009] [PMID: 19279265]
[5]
Vasile F, Dossi E, Rouach N. Human astrocytes: Structure and functions in the healthy brain. Brain Struct Funct 2017; 222(5): 2017-29.
[http://dx.doi.org/10.1007/s00429-017-1383-5] [PMID: 28280934]
[6]
MacVicar BA, Newman EA. Astrocyte regulation of blood flow in the brain. Cold Spring Harb Perspect Biol 2015; 7(5): a020388.
[http://dx.doi.org/10.1101/cshperspect.a020388] [PMID: 25818565]
[7]
Ventura R, Harris KM. Three-dimensional relationships between hippocampal synapses and astrocytes. J Neurosci 1999; 19(16): 6897-906.
[http://dx.doi.org/10.1523/JNEUROSCI.19-16-06897.1999] [PMID: 10436047]
[8]
Grosche J, Matyash V, Möller T, Verkhratsky A, Reichenbach A, Kettenmann H. Microdomains for neuron-glia interaction: Parallel fiber signaling to Bergmann glial cells. Nat Neurosci 1999; 2(2): 139-43.
[http://dx.doi.org/10.1038/5692] [PMID: 10195197]
[9]
Grosche J, Kettenmann H, Reichenbach A. Bergmann glial cells form distinct morphological structures to interact with cerebellar neurons. J Neurosci Res 2002; 68(2): 138-49.
[http://dx.doi.org/10.1002/jnr.10197] [PMID: 11948659]
[10]
Araque A, Parpura V, Sanzgiri RP, Haydon PG. Tripartite synapses: Glia, the unacknowledged partner. Trends Neurosci 1999; 22(5): 208-15.
[http://dx.doi.org/10.1016/S0166-2236(98)01349-6] [PMID: 10322493]
[11]
Farhy-Tselnicker I, Allen NJ. Astrocytes, neurons, synapses: A tripartite view on cortical circuit development. Neural Dev 2018; 13(1): 7.
[http://dx.doi.org/10.1186/s13064-018-0104-y] [PMID: 29712572]
[12]
Farmer WT, Murai K. Resolving astrocyte heterogeneity in the CNS. Front Cell Neurosci 2017; 11: 300.
[http://dx.doi.org/10.3389/fncel.2017.00300] [PMID: 29021743]
[13]
Matias I, Morgado J, Gomes FCA. Astrocyte heterogeneity: Impact to brain aging and disease. Front Aging Neurosci 2019; 11: 59.
[http://dx.doi.org/10.3389/fnagi.2019.00059] [PMID: 30941031]
[14]
Morel L, Chiang MSR, Higashimori H, et al. Molecular and functional properties of regional astrocytes in the adult brain. J Neurosci 2017; 37(36): 8706-17.
[http://dx.doi.org/10.1523/JNEUROSCI.3956-16.2017] [PMID: 28821665]
[15]
Batiuk MY, Martirosyan A, Wahis J, et al. Identification of region-specific astrocyte subtypes at single cell resolution. Nat Commun 2020; 11(1): 1220.
[http://dx.doi.org/10.1038/s41467-019-14198-8] [PMID: 32139688]
[16]
Yeh TH, Lee DY, Gianino SM, Gutmann DH. Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)-regulated glial proliferation. Glia 2009; 57(11): 1239-49.
[http://dx.doi.org/10.1002/glia.20845] [PMID: 19191334]
[17]
Chai H, Diaz-Castro B, Shigetomi E, et al. Neural circuit-specialized astrocytes: Transcriptomic, proteomic, morphological, and functional evidence. Neuron 2017; 95(3): 531-549.e9.
[http://dx.doi.org/10.1016/j.neuron.2017.06.029] [PMID: 28712653]
[18]
Srinivasan R, Lu TY, Chai H, et al. New transgenic mouse lines for selectively targeting astrocytes and studying calcium signals in astrocyte processes in situ and in vivo. Neuron 2016; 92(6): 1181-95.
[http://dx.doi.org/10.1016/j.neuron.2016.11.030] [PMID: 27939582]
[19]
Xin W, Schuebel KE, Jair K, et al. Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling. Neuropsychopharmacology 2019; 44(2): 344-55.
[http://dx.doi.org/10.1038/s41386-018-0151-4] [PMID: 30054584]
[20]
Chung WS, Allen NJ, Eroglu C. Astrocytes control synapse formation, function, and elimination. Cold Spring Harb Perspect Biol 2015; 7(9): a020370.
[http://dx.doi.org/10.1101/cshperspect.a020370] [PMID: 25663667]
[21]
Ullian EM, Sapperstein SK, Christopherson KS, Barres BA. Control of synapse number by glia. Science 2001; 291(5504): 657-61.
[http://dx.doi.org/10.1126/science.291.5504.657] [PMID: 11158678]
[22]
Diniz LP, Tortelli V, Garcia MN, et al. Astrocyte transforming growth factor beta 1 promotes inhibitory synapse formation via CaM kinase II signaling. Glia 2014; 62(12): 1917-31.
[http://dx.doi.org/10.1002/glia.22713] [PMID: 25042347]
[23]
Baldwin KT, Eroglu C. Molecular mechanisms of astrocyte-induced synaptogenesis. Curr Opin Neurobiol 2017; 45: 113-20.
[http://dx.doi.org/10.1016/j.conb.2017.05.006] [PMID: 28570864]
[24]
Blanco-Suárez E, Caldwell ALM, Allen NJ. Role of astrocyte-synapse interactions in CNS disorders. J Physiol 2017; 595(6): 1903-16.
[http://dx.doi.org/10.1113/JP270988] [PMID: 27381164]
[25]
Chung WS, Clarke LE, Wang GX, et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature 2013; 504(7480): 394-400.
[http://dx.doi.org/10.1038/nature12776] [PMID: 24270812]
[26]
Noriega-Prieto JA, Araque A. Sensing and regulating synaptic activity by astrocytes at tripartite synapse. Neurochem Res 2021; 46(10): 2580-5.
[http://dx.doi.org/10.1007/s11064-021-03317-x] [PMID: 33837868]
[27]
Durkee CA, Araque A. Diversity and specificity of astrocyte-neuron communication. Neuroscience 2019; 396: 73-8.
[http://dx.doi.org/10.1016/j.neuroscience.2018.11.010] [PMID: 30458223]
[28]
Heithoff BP, George KK, Phares AN, Zuidhoek IA, Munoz-Ballester C, Robel S. Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain. Glia 2021; 69(2): 436-72.
[http://dx.doi.org/10.1002/glia.23908] [PMID: 32955153]
[29]
Salhia B, Angelov L, Roncari L, Wu X, Shannon P, Guha A. Expression of vascular endothelial growth factor by reactive astrocytes and associated neoangiogenesis. Brain Res 2000; 883(1): 87-97.
[http://dx.doi.org/10.1016/S0006-8993(00)02825-0] [PMID: 11063991]
[30]
Howarth C. The contribution of astrocytes to the regulation of cerebral blood flow. Front Neurosci 2014; 8: 103.
[http://dx.doi.org/10.3389/fnins.2014.00103] [PMID: 24847203]
[31]
Schousboe A, Bak LK, Waagepetersen HS. Astrocytic control of biosynthesis and turnover of the neurotransmitters glutamate and GABA. Front Endocrinol 2013; 4: 102.
[http://dx.doi.org/10.3389/fendo.2013.00102] [PMID: 23966981]
[32]
Mederos S, González-Arias C, Perea G. Astrocyte-neuron networks: A multilane highway of signaling for homeostatic brain function. Front Synaptic Neurosci 2018; 10: 45.
[http://dx.doi.org/10.3389/fnsyn.2018.00045] [PMID: 30542276]
[33]
Petr GT, Sun Y, Frederick NM, et al. Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes. J Neurosci 2015; 35(13): 5187-201.
[http://dx.doi.org/10.1523/JNEUROSCI.4255-14.2015] [PMID: 25834045]
[34]
Evans RD, Brown AM, Ransom BR. Glycogen function in adult central and peripheral nerves. J Neurosci Res 2013; 91(8): 1044-9.
[http://dx.doi.org/10.1002/jnr.23229] [PMID: 23633387]
[35]
Chuquet J, Quilichini P, Nimchinsky EA, Buzsáki G. Predominant enhancement of glucose uptake in astrocytes versus neurons during activation of the somatosensory cortex. J Neurosci 2010; 30(45): 15298-303.
[http://dx.doi.org/10.1523/JNEUROSCI.0762-10.2010] [PMID: 21068334]
[36]
Magistretti PJ, Allaman I. Lactate in the brain: From metabolic end-product to signalling molecule. Nat Rev Neurosci 2018; 19(4): 235-49.
[http://dx.doi.org/10.1038/nrn.2018.19] [PMID: 29515192]
[37]
Berthet C, Lei H, Thevenet J, Gruetter R, Magistretti PJ, Hirt L. Neuroprotective role of lactate after cerebral ischemia. J Cereb Blood Flow Metab 2009; 29(11): 1780-9.
[http://dx.doi.org/10.1038/jcbfm.2009.97] [PMID: 19675565]
[38]
Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 2004; 305(5680): 99-103.
[http://dx.doi.org/10.1126/science.1096485] [PMID: 15232110]
[39]
Esteras N, Dinkova-Kostova AT, Abramov AY. Nrf2 activation in the treatment of neurodegenerative diseases: A focus on its role in mitochondrial bioenergetics and function. Biol Chem 2016; 397(5): 383-400.
[http://dx.doi.org/10.1515/hsz-2015-0295] [PMID: 26812787]
[40]
Bell KFS, Fowler JH, Al-Mubarak B, Horsburgh K, Hardingham GE. Activation of Nrf2-regulated glutathione pathway genes by ischemic preconditioning. Oxid Med Cell Longev 2011; 2011: 1-7.
[http://dx.doi.org/10.1155/2011/689524] [PMID: 21904646]
[41]
Dringen R, Gutterer JM, Hirrlinger J. Glutathione metabolism in brain. Eur J Biochem 2000; 267(16): 4912-6.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01597.x] [PMID: 10931173]
[42]
Jimenez-Blasco D, Santofimia-Castaño P, Gonzalez A, Almeida A, Bolaños JP. Astrocyte NMDA receptors’ activity sustains neuronal survival through a Cdk5-Nrf2 pathway. Cell Death Differ 2015; 22(11): 1877-89.
[http://dx.doi.org/10.1038/cdd.2015.49] [PMID: 25909891]
[43]
Colangelo AM, Alberghina L, Papa M. Astrogliosis as a therapeutic target for neurodegenerative diseases. Neurosci Lett 2014; 565: 59-64.
[http://dx.doi.org/10.1016/j.neulet.2014.01.014] [PMID: 24457173]
[44]
Sofroniew MV. Astrocyte reactivity: Subtypes, states, and functions in cns innate immunity. Trends Immunol 2020; 41(9): 758-70.
[http://dx.doi.org/10.1016/j.it.2020.07.004] [PMID: 32819810]
[45]
Escartin C, Galea E, Lakatos A, et al. Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci 2021; 24(3): 312-25.
[http://dx.doi.org/10.1038/s41593-020-00783-4] [PMID: 33589835]
[46]
Santello M, Volterra A. TNFα in synaptic function: Switching gears. Trends Neurosci 2012; 35(10): 638-47.
[http://dx.doi.org/10.1016/j.tins.2012.06.001] [PMID: 22749718]
[47]
Liddelow SA, Guttenplan KA, Clarke LE, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017; 541(7638): 481-7.
[http://dx.doi.org/10.1038/nature21029] [PMID: 28099414]
[48]
Wanner IB, Anderson MA, Song B, et al. Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci 2013; 33(31): 12870-86.
[http://dx.doi.org/10.1523/JNEUROSCI.2121-13.2013] [PMID: 23904622]
[49]
Bush TG, Puvanachandra N, Horner CH, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 1999; 23(2): 297-308.
[http://dx.doi.org/10.1016/S0896-6273(00)80781-3] [PMID: 10399936]
[50]
Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 2004; 24(9): 2143-55.
[http://dx.doi.org/10.1523/JNEUROSCI.3547-03.2004] [PMID: 14999065]
[51]
Schwartz JP, Nishiyama N. Neurotrophic factor gene expression in astrocytes during development and following injury. Brain Res Bull 1994; 35(5-6): 403-7.
[http://dx.doi.org/10.1016/0361-9230(94)90151-1] [PMID: 7532097]
[52]
März P, Heese K, Dimitriades-Schmutz B, Rose-John S, Otten U. Role of interleukin‐6 and soluble IL‐6 receptor in region‐specific induction of astrocytic differentiation and neurotrophin expression. Glia 1999; 26(3): 191-200.
[http://dx.doi.org/10.1002/(SICI)1098-1136(199905)26:3<191::AID-GLIA1>3.0.CO;2-#] [PMID: 10340760]
[53]
Miyamoto N, Maki T, Shindo A, et al. astrocytes promote oligodendrogenesis after white matter damage via brain-derived neurotrophic factor. J Neurosci 2015; 35(41): 14002-8.
[http://dx.doi.org/10.1523/JNEUROSCI.1592-15.2015] [PMID: 26468200]
[54]
Teh DBL, Prasad A, Jiang W, et al. Transcriptome analysis reveals neuroprotective aspects of human reactive astrocytes induced by interleukin 1β. Sci Rep 2017; 7(1): 13988.
[http://dx.doi.org/10.1038/s41598-017-13174-w] [PMID: 29070875]
[55]
Datta I, Ganapathy K, Razdan R, Bhonde R. Location and number of astrocytes determine dopaminergic neuron survival and function under 6-OHDA stress mediated through differential BDNF release. Mol Neurobiol 2018; 55(7): 5505-25.
[http://dx.doi.org/10.1007/s12035-017-0767-0] [PMID: 28965325]
[56]
Guescini M, Genedani S, Stocchi V, Agnati LF. Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J Neural Transm 2010; 117(1): 1-4.
[http://dx.doi.org/10.1007/s00702-009-0288-8] [PMID: 19680595]
[57]
Upadhya R, Zingg W, Shetty S, Shetty AK. Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders. J Control Release 2020; 323: 225-39.
[http://dx.doi.org/10.1016/j.jconrel.2020.04.017] [PMID: 32289328]
[58]
Wang G, Dinkins M, He Q, et al. Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): Potential mechanism of apoptosis induction in Alzheimer disease (AD). J Biol Chem 2012; 287(25): 21384-95.
[http://dx.doi.org/10.1074/jbc.M112.340513] [PMID: 22532571]
[59]
Guitart K, Loers G, Buck F, Bork U, Schachner M, Kleene R. Improvement of neuronal cell survival by astrocyte-derived exosomes under hypoxic and ischemic conditions depends on prion protein. Glia 2016; 64(6): 22963.
[http://dx.doi.org/10.1002/glia.22963] [PMID: 26992135]
[60]
Davis CO, Marsh-Armstrong N. Discovery and implications of transcellular mitophagy. Autophagy 2014; 10(12): 2383-4.
[http://dx.doi.org/10.4161/15548627.2014.981920] [PMID: 25484086]
[61]
Nguyen TT, Oh SS, Weaver D, et al. Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease. Proc Natl Acad Sci 2014; 111(35): E3631-40.
[http://dx.doi.org/10.1073/pnas.1402449111] [PMID: 25136135]
[62]
Hayakawa K, Esposito E, Wang X, et al. Transfer of mitochondria from astrocytes to neurons after stroke. Nature 2016; 535(7613): 551-5.
[http://dx.doi.org/10.1038/nature18928] [PMID: 27466127]
[63]
Parpura V, Verkhratsky A. Homeostatic function of astrocytes: Ca2+ and Na+ signalling. Transl Neurosci 2012; 3(4): 334-44.
[http://dx.doi.org/10.2478/s13380-012-0040-y] [PMID: 23243501]
[64]
Pajarillo E, Rizor A, Lee J, Aschner M, Lee E. The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics. Neuropharmacology 2019; 161: 107559.
[http://dx.doi.org/10.1016/j.neuropharm.2019.03.002] [PMID: 30851309]
[65]
Andersen JV, Schousboe A. Milestone Review: Metabolic dynamics of glutamate and GABA mediated neurotransmission - The essential roles of astrocytes. J Neurochem 2023; 166(2): 109-37.
[http://dx.doi.org/10.1111/jnc.15811]
[66]
Almeida A, Jimenez-Blasco D, Bolaños JP. Cross-talk between energy and redox metabolism in astrocyte-neuron functional cooperation. Essays Biochem 2023; 67(1): 17-26.
[http://dx.doi.org/10.1042/EBC20220075] [PMID: 36805653]
[67]
Ben Haim L, Carrillo-de Sauvage MA, Ceyzériat K, Escartin C. Elusive roles for reactive astrocytes in neurodegenerative diseases. Front Cell Neurosci 2015; 9: 278.
[http://dx.doi.org/10.3389/fncel.2015.00278] [PMID: 26283915]
[68]
Park J, Chung WS. Astrocyte-dependent circuit remodeling by synapse phagocytosis. Curr Opin Neurobiol 2023; 81: 102732.
[http://dx.doi.org/10.1016/j.conb.2023.102732] [PMID: 37247606]
[69]
Dong LF, Rohlena J, Zobalova R, et al. Mitochondria on the move: Horizontal mitochondrial transfer in disease and health. J Cell Biol 2023; 222(3): e202211044.
[http://dx.doi.org/10.1083/jcb.202211044] [PMID: 36795453]
[70]
Verkhratsky A, Parpura V. Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders. Neurobiol Dis 2016; 85: 254-61.
[http://dx.doi.org/10.1016/j.nbd.2015.03.025] [PMID: 25843667]
[71]
Maragakis NJ, Rothstein JD. Mechanisms of Disease: Astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2006; 2(12): 679-89.
[http://dx.doi.org/10.1038/ncpneuro0355] [PMID: 17117171]
[72]
Rossi D. Astrocyte physiopathology: At the crossroads of intercellular networking, inflammation and cell death. Prog Neurobiol 2015; 130: 86-120.
[http://dx.doi.org/10.1016/j.pneurobio.2015.04.003] [PMID: 25930681]
[73]
Yun SP, Kam TI, Panicker N, et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease. Nat Med 2018; 24(7): 931-8.
[http://dx.doi.org/10.1038/s41591-018-0051-5] [PMID: 29892066]
[74]
Sofroniew MV. Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci 2015; 16(5): 249-63.
[http://dx.doi.org/10.1038/nrn3898] [PMID: 25891508]
[75]
Anderson MA, Burda JE, Ren Y, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature 2016; 532(7598): 195-200.
[http://dx.doi.org/10.1038/nature17623] [PMID: 27027288]
[76]
Nagai M, Re DB, Nagata T, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 2007; 10(5): 615-22.
[http://dx.doi.org/10.1038/nn1876] [PMID: 17435755]
[77]
Haidet-Phillips AM, Hester ME, Miranda CJ, et al. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol 2011; 29(9): 824-8.
[http://dx.doi.org/10.1038/nbt.1957] [PMID: 21832997]
[78]
Clement AM, Nguyen MD, Roberts EA, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 2003; 302(5642): 113-7.
[http://dx.doi.org/10.1126/science.1086071] [PMID: 14526083]
[79]
Kawamata H, Ng SK, Diaz N, et al. Abnormal intracellular calcium signaling and SNARE-dependent exocytosis contributes to SOD1G93A astrocyte-mediated toxicity in amyotrophic lateral sclerosis. J Neurosci 2014; 34(6): 2331-48.
[http://dx.doi.org/10.1523/JNEUROSCI.2689-13.2014] [PMID: 24501372]
[80]
Meyer K, Ferraiuolo L, Miranda CJ, et al. Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS. Proc Natl Acad Sci 2014; 111(2): 829-32.
[http://dx.doi.org/10.1073/pnas.1314085111] [PMID: 24379375]
[81]
Re DB, Le Verche V, Yu C, et al. Necroptosis drives motor neuron death in models of both sporadic and familial ALS. Neuron 2014; 81(5): 1001-8.
[http://dx.doi.org/10.1016/j.neuron.2014.01.011] [PMID: 24508385]
[82]
Papadeas ST, Kraig SE, O’Banion C, Lepore AC, Maragakis NJ. Astrocytes carrying the superoxide dismutase 1 (SOD1 G93A) mutation induce wild-type motor neuron degeneration in vivo. Proc Natl Acad Sci 2011; 108(43): 17803-8.
[http://dx.doi.org/10.1073/pnas.1103141108] [PMID: 21969586]
[83]
Kia A, McAvoy K, Krishnamurthy K, Trotti D, Pasinelli P. Astrocytes expressing ALS-linked mutant FUS induce motor neuron death through release of tumor necrosis factor-alpha. Glia 2018; 66(5): 1016-33.
[http://dx.doi.org/10.1002/glia.23298] [PMID: 29380416]
[84]
Díaz-Amarilla P, Olivera-Bravo S, Trias E, et al. Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis. Proc Natl Acad Sci 2011; 108(44): 18126-31.
[http://dx.doi.org/10.1073/pnas.1110689108] [PMID: 22010221]
[85]
Trias E, Ibarburu S, Barreto-Núñez R, Barbeito L. Significance of aberrant glial cell phenotypes in pathophysiology of amyotrophic lateral sclerosis. Neurosci Lett 2017; 636: 27-31.
[http://dx.doi.org/10.1016/j.neulet.2016.07.052] [PMID: 27473942]
[86]
Peng AYT, Agrawal I, Ho WY, et al. Loss of TDP-43 in astrocytes leads to motor deficits by triggering A1-like reactive phenotype and triglial dysfunction. Proc Natl Acad Sci 2020; 117(46): 29101-12.
[http://dx.doi.org/10.1073/pnas.2007806117] [PMID: 33127758]
[87]
Birger A, Ben-Dor I, Ottolenghi M, et al. Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity. EBioMedicine 2019; 50: 274-89.
[http://dx.doi.org/10.1016/j.ebiom.2019.11.026] [PMID: 31787569]
[88]
Guttenplan KA, Weigel MK, Adler DI, et al. Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model. Nat Commun 2020; 11(1): 3753.
[http://dx.doi.org/10.1038/s41467-020-17514-9] [PMID: 32719333]
[89]
Gomes C, Sequeira C, Likhite S, et al. Neurotoxic Astrocytes Directly Converted from Sporadic and Familial ALS patient fibroblasts reveal signature diversities and MIR-146a theragnostic potential in specific subtypes. Cells 2022; 11(7): 1186.
[http://dx.doi.org/10.3390/cells11071186] [PMID: 35406750]
[90]
Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 2005; 171(6): 1001-12.
[http://dx.doi.org/10.1083/jcb.200508072] [PMID: 16365166]
[91]
Bates GP, Dorsey R, Gusella JF, et al. Huntington disease. Nat Rev Dis Primers 2015; 1(1): 15005.
[http://dx.doi.org/10.1038/nrdp.2015.5] [PMID: 27188817]
[92]
Faideau M, Kim J, Cormier K, et al. In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: A correlation with Huntington’s disease subjects. Hum Mol Genet 2010; 19(15): 3053-67.
[http://dx.doi.org/10.1093/hmg/ddq212] [PMID: 20494921]
[93]
Hsiao HY, Chen YC, Chen HM, Tu PH, Chern Y. A critical role of astrocyte-mediated nuclear factor-κB-dependent inflammation in Huntington’s disease. Hum Mol Genet 2013; 22(9): 1826-42.
[http://dx.doi.org/10.1093/hmg/ddt036] [PMID: 23372043]
[94]
Bradford J, Shin JY, Roberts M, Wang CE, Li XJ, Li S. Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci 2009; 106(52): 22480-5.
[http://dx.doi.org/10.1073/pnas.0911503106] [PMID: 20018729]
[95]
Bradford J, Shin JY, Roberts M, et al. Mutant huntingtin in glial cells exacerbates neurological symptoms of Huntington disease mice. J Biol Chem 2010; 285(14): 10653-61.
[http://dx.doi.org/10.1074/jbc.M109.083287] [PMID: 20145253]
[96]
Tong X, Ao Y, Faas GC, et al. Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington’s disease model mice. Nat Neurosci 2014; 17(5): 694-703.
[http://dx.doi.org/10.1038/nn.3691] [PMID: 24686787]
[97]
Abjean L, Ben Haim L, Riquelme-Perez M, et al. Reactive astrocytes promote proteostasis in Huntington’s disease through the JAK2-STAT3 pathway. Brain 2023; 146(1): 149-66.
[http://dx.doi.org/10.1093/brain/awac068] [PMID: 35298632]
[98]
Browne SE, Bowling AC, Macgarvey U, et al. Oxidative damage and metabolic dysfunction in Huntington’s disease: Selective vulnerability of the basal ganglia. Ann Neurol 1997; 41(5): 646-53.
[http://dx.doi.org/10.1002/ana.410410514] [PMID: 9153527]
[99]
Damiano M, Diguet E, Malgorn C, et al. A role of mitochondrial complex II defects in genetic models of Huntington’s disease expressing N-terminal fragments of mutant huntingtin. Hum Mol Genet 2013; 22(19): 3869-82.
[http://dx.doi.org/10.1093/hmg/ddt242] [PMID: 23720495]
[100]
Brouillet E, Jacquard C, Bizat N, Blum D. 3-Nitropropionic acid: A mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington’s disease. J Neurochem 2005; 95(6): 1521-40.
[http://dx.doi.org/10.1111/j.1471-4159.2005.03515.x] [PMID: 16300642]
[101]
Misiak M, Singh S, Drewlo S, Beyer C, Arnold S. Brain region-specific vulnerability of astrocytes in response to 3-nitropropionic acid is mediated by cytochrome c oxidase isoform expression. Cell Tissue Res 2010; 341(1): 83-93.
[http://dx.doi.org/10.1007/s00441-010-0995-3] [PMID: 20602186]
[102]
Polyzos AA, Lee DY, Datta R, et al. Metabolic reprogramming in astrocytes distinguishes region-specific neuronal susceptibility in huntington mice. Cell Metab 2019; 29(6): 1258.e11.
[http://dx.doi.org/10.1016/j.cmet.2019.03.004] [PMID: 30930170]
[103]
Boussicault L, Hérard AS, Calingasan N, et al. Impaired brain energy metabolism in the BACHD mouse model of Huntington’s disease: Critical role of astrocyte-neuron interactions. J Cereb Blood Flow Metab 2014; 34(9): 1500-10.
[http://dx.doi.org/10.1038/jcbfm.2014.110] [PMID: 24938402]
[104]
Ehrnhoefer DE, Southwell AL, Sivasubramanian M, et al. HACE1 is essential for astrocyte mitochondrial function and influences Huntington disease phenotypes in vivo. Hum Mol Genet 2018; 27(2): 239-53.
[http://dx.doi.org/10.1093/hmg/ddx394] [PMID: 29121340]
[105]
Jang M, Choi JH, Chang Y, Lee SJ, Nah SY, Cho IH. Gintonin, a ginseng-derived ingredient, as a novel therapeutic strategy for Huntington’s disease: Activation of the Nrf2 pathway through lysophosphatidic acid receptors. Brain Behav Immun 2019; 80: 146-62.
[http://dx.doi.org/10.1016/j.bbi.2019.03.001] [PMID: 30853569]
[106]
Lopez-Sanchez C, Garcia-Martinez V, Poejo J, Garcia-Lopez V, Salazar J, Gutierrez-Merino C. Early reactive a1 astrocytes induction by the neurotoxin 3-nitropropionic acid in rat brain. Int J Mol Sci 2020; 21(10): 3609.
[http://dx.doi.org/10.3390/ijms21103609] [PMID: 32443829]
[107]
Saba J, López Couselo F, Turati J, et al. Astrocytes from cortex and striatum show differential responses to mitochondrial toxin and BDNF: Implications for protection of striatal neurons expressing mutant huntingtin. J Neuroinflammation 2020; 17(1): 290.
[http://dx.doi.org/10.1186/s12974-020-01965-4] [PMID: 33023623]
[108]
Zuccato C, Marullo M, Conforti P, MacDonald ME, Tartari M, Cattaneo E. Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington’s disease. Brain Pathol 2008; 18(2): 225-38.
[http://dx.doi.org/10.1111/j.1750-3639.2007.00111.x] [PMID: 18093249]
[109]
Wang L, Lin F, Wang J, et al. Expression of mutant N-terminal huntingtin fragment (htt552-100Q) in astrocytes suppresses the secretion of BDNF. Brain Res 2012; 1449: 69-82.
[http://dx.doi.org/10.1016/j.brainres.2012.01.077] [PMID: 22410294]
[110]
Hong Y, Zhao T, Li XJ, Li S. Mutant huntingtin impairs BDNF release from astrocytes by disrupting conversion of Rab3a-GTP into Rab3a-GDP. J Neurosci 2016; 36(34): 8790-801.
[http://dx.doi.org/10.1523/JNEUROSCI.0168-16.2016] [PMID: 27559163]
[111]
Xie Y, Hayden MR, Xu B. BDNF overexpression in the forebrain rescues Huntington’s disease phenotypes in YAC128 mice. J Neurosci 2010; 30(44): 14708-18.
[http://dx.doi.org/10.1523/JNEUROSCI.1637-10.2010] [PMID: 21048129]
[112]
Gharami K, Xie Y, An JJ, Tonegawa S, Xu B. Brain-derived neurotrophic factor over-expression in the forebrain ameliorates Huntington’s disease phenotypes in mice. J Neurochem 2008; 105(2): 369-79.
[http://dx.doi.org/10.1111/j.1471-4159.2007.05137.x] [PMID: 18086127]
[113]
Reick C, Ellrichmann G, Tsai T, et al. Expression of brain-derived neurotrophic factor in astrocytes - Beneficial effects of glatiramer acetate in the R6/2 and YAC128 mouse models of Huntington's disease. Exp Neurol 2016; 285(Pt A): 12-33.
[114]
Giralt A, Carretón O, Lao-Peregrin C, Martín ED, Alberch J. Conditional BDNF release under pathological conditions improves Huntington’s disease pathology by delaying neuronal dysfunction. Mol Neurodegener 2011; 6(1): 71.
[http://dx.doi.org/10.1186/1750-1326-6-71] [PMID: 21985529]
[115]
Diaz-Castro B, Gangwani MR, Yu X, Coppola G, Khakh BS. Astrocyte molecular signatures in Huntington’s disease. Sci Transl Med 2019; 11(514): eaaw8546.
[http://dx.doi.org/10.1126/scitranslmed.aaw8546] [PMID: 31619545]
[116]
Benraiss A, Mariani JN, Osipovitch M, et al. Cell-intrinsic glial pathology is conserved across human and murine models of Huntington’s disease. Cell Rep 2021; 36(1): 109308.
[http://dx.doi.org/10.1016/j.celrep.2021.109308] [PMID: 34233199]
[117]
Booth HDE, Hirst WD, Wade-Martins R. The role of astrocyte dysfunction in parkinson’s disease pathogenesis. Trends Neurosci 2017; 40(6): 358-70.
[http://dx.doi.org/10.1016/j.tins.2017.04.001] [PMID: 28527591]
[118]
Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers 2017; 3(1): 17013.
[http://dx.doi.org/10.1038/nrdp.2017.13] [PMID: 28332488]
[119]
Braak H, Sastre M, Del Tredici K. Development of α-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson’s disease. Acta Neuropathol 2007; 114(3): 231-41.
[http://dx.doi.org/10.1007/s00401-007-0244-3] [PMID: 17576580]
[120]
Braidy N, Gai WP, Xu YH, et al. Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes, cortical neurons and fibroblasts. Transl Neurodegener 2013; 2(1): 20.
[http://dx.doi.org/10.1186/2047-9158-2-20] [PMID: 24093918]
[121]
Lee HJ, Suk JE, Patrick C, et al. Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 2010; 285(12): 9262-72.
[http://dx.doi.org/10.1074/jbc.M109.081125] [PMID: 20071342]
[122]
Rannikko EH, Weber SS, Kahle PJ. Exogenous α-synuclein induces toll-like receptor 4 dependent inflammatory responses in astrocytes. BMC Neurosci 2015; 16(1): 57.
[http://dx.doi.org/10.1186/s12868-015-0192-0] [PMID: 26346361]
[123]
Barnum CJ, Chen X, Chung J, et al. Peripheral administration of the selective inhibitor of soluble tumor necrosis factor (TNF) XPro®1595 attenuates nigral cell loss and glial activation in 6-OHDA hemiparkinsonian rats. J Parkinsons Dis 2014; 4(3): 349-60.
[http://dx.doi.org/10.3233/JPD-140410] [PMID: 25061061]
[124]
McCoy MK, Martinez TN, Ruhn KA, et al. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson’s disease. J Neurosci 2006; 26(37): 9365-75.
[http://dx.doi.org/10.1523/JNEUROSCI.1504-06.2006] [PMID: 16971520]
[125]
Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H. Astrocytic expression of Parkinson’s disease-related A53T α-synuclein causes neurodegeneration in mice. Mol Brain 2010; 3(1): 12.
[http://dx.doi.org/10.1186/1756-6606-3-12] [PMID: 20409326]
[126]
Yang Y, Song JJ, Choi YR, et al. Therapeutic functions of astrocytes to treat α-synuclein pathology in Parkinson’s disease. Proc Natl Acad Sci 2022; 119(29): e2110746119.
[http://dx.doi.org/10.1073/pnas.2110746119] [PMID: 35858361]
[127]
Bandopadhyay R, Kingsbury AE, Cookson MR, et al. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain 2004; 127(2): 420-30.
[http://dx.doi.org/10.1093/brain/awh054] [PMID: 14662519]
[128]
Mullett SJ, Hinkle DA. DJ-1 knock-down in astrocytes impairs astrocyte-mediated neuroprotection against rotenone. Neurobiol Dis 2009; 33(1): 28-36.
[http://dx.doi.org/10.1016/j.nbd.2008.09.013] [PMID: 18930142]
[129]
Mullett SJ, Di Maio R, Greenamyre JT, Hinkle DA. DJ-1 expression modulates astrocyte-mediated protection against neuronal oxidative stress. J Mol Neurosci 2013; 49(3): 507-11.
[http://dx.doi.org/10.1007/s12031-012-9904-4] [PMID: 23065353]
[130]
Brück D, Wenning GK, Stefanova N, Fellner L. Glia and alpha-synuclein in neurodegeneration: A complex interaction. Neurobiol Dis 2016; 85: 262-74.
[http://dx.doi.org/10.1016/j.nbd.2015.03.003] [PMID: 25766679]
[131]
Chavarría C, Rodríguez-Bottero S, Quijano C, Cassina P, Souza JM. Impact of monomeric, oligomeric and fibrillar alpha-synuclein on astrocyte reactivity and toxicity to neurons. Biochem J 2018; 475(19): 3153-69.
[http://dx.doi.org/10.1042/BCJ20180297] [PMID: 30185433]
[132]
Ramos-Gonzalez P, Mato S, Chara JC, Verkhratsky A, Matute C, Cavaliere F. Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation. NPJ Parkinsons Dis 2021; 7(1): 31.
[http://dx.doi.org/10.1038/s41531-021-00175-w] [PMID: 33785762]
[133]
Atri A. the alzheimer’s disease clinical spectrum. Med Clin North Am 2019; 103(2): 263-93.
[http://dx.doi.org/10.1016/j.mcna.2018.10.009] [PMID: 30704681]
[134]
Owen JB, Di Domenico F, Sultana R, et al. Proteomics-determined differences in the concanavalin-A-fractionated proteome of hippocampus and inferior parietal lobule in subjects with Alzheimer’s disease and mild cognitive impairment: Implications for progression of AD. J Proteome Res 2009; 8(2): 471-82.
[http://dx.doi.org/10.1021/pr800667a] [PMID: 19072283]
[135]
Carter SF, Schöll M, Almkvist O, et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: A multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med 2012; 53(1): 37-46.
[http://dx.doi.org/10.2967/jnumed.110.087031] [PMID: 22213821]
[136]
Heneka MT, Sastre M, Dumitrescu-Ozimek L, et al. Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice. J Neuroinflammation 2005; 2(1): 22.
[http://dx.doi.org/10.1186/1742-2094-2-22] [PMID: 16212664]
[137]
Abeti R, Abramov AY, Duchen MR. β-amyloid activates PARP causing astrocytic metabolic failure and neuronal death. Brain 2011; 134(6): 1658-72.
[http://dx.doi.org/10.1093/brain/awr104] [PMID: 21616968]
[138]
Chun H, Im H, Kang YJ, et al. Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production. Nat Neurosci 2020; 23(12): 1555-66.
[http://dx.doi.org/10.1038/s41593-020-00735-y] [PMID: 33199896]
[139]
Oksanen M, Petersen AJ, Naumenko N, et al. PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in alzheimer’s disease. Stem Cell Reports 2017; 9(6): 1885-97.
[http://dx.doi.org/10.1016/j.stemcr.2017.10.016] [PMID: 29153989]
[140]
Katsouri L, Birch AM, Renziehausen AWJ, et al. Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer’s disease. Glia 2020; 68(5): 1017-30.
[http://dx.doi.org/10.1002/glia.23759] [PMID: 31799735]
[141]
Nagele RG, D’Andrea MR, Lee H, Venkataraman V, Wang HY. Astrocytes accumulate Aβ42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res 2003; 971(2): 197-209.
[http://dx.doi.org/10.1016/S0006-8993(03)02361-8] [PMID: 12706236]
[142]
Matos M, Augusto E, Machado NJ, dos Santos-Rodrigues A, Cunha RA, Agostinho P. Astrocytic adenosine A2A receptors control the amyloid-β peptide-induced decrease of glutamate uptake. J Alzheimers Dis 2012; 31(3): 555-67.
[http://dx.doi.org/10.3233/JAD-2012-120469] [PMID: 22647260]
[143]
Matos M, Augusto E, Oliveira CR, Agostinho P. Amyloid-beta peptide decreases glutamate uptake in cultured astrocytes: Involvement of oxidative stress and mitogen-activated protein kinase cascades. Neuroscience 2008; 156(4): 898-910.
[http://dx.doi.org/10.1016/j.neuroscience.2008.08.022] [PMID: 18790019]
[144]
Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ. Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 2009; 323(5918): 1211-5.
[http://dx.doi.org/10.1126/science.1169096] [PMID: 19251629]
[145]
Orellana JA, Shoji KF, Abudara V, et al. Amyloid β-induced death in neurons involves glial and neuronal hemichannels. J Neurosci 2011; 31(13): 4962-77.
[http://dx.doi.org/10.1523/JNEUROSCI.6417-10.2011] [PMID: 21451035]
[146]
Goetzl EJ, Mustapic M, Kapogiannis D, et al. Cargo proteins of plasma astrocyte‐derived exosomes in Alzheimer’s disease. FASEB J 2016; 30(11): 3853-9.
[http://dx.doi.org/10.1096/fj.201600756R] [PMID: 27511944]
[147]
Liu CC, Kanekiyo T, Xu H, Bu G, Bu G. Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nat Rev Neurol 2013; 9(2): 106-18.
[http://dx.doi.org/10.1038/nrneurol.2012.263] [PMID: 23296339]
[148]
Zhao J, Davis MD, Martens YA, et al. APOE ε4/ε4 diminishes neurotrophic function of human iPSC-derived astrocytes. Hum Mol Genet 2017; 26(14): 2690-700.
[http://dx.doi.org/10.1093/hmg/ddx155] [PMID: 28444230]
[149]
Wang C, Xiong M, Gratuze M, et al. Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia. Neuron 2021; 109(10): 1657-74.
[http://dx.doi.org/10.1016/j.neuron.2021.03.024]
[150]
Koistinaho M, Lin S, Wu X, et al. Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-β peptides. Nat Med 2004; 10(7): 719-26.
[http://dx.doi.org/10.1038/nm1058] [PMID: 15195085]
[151]
Liu CC, Zhao N, Fu Y, et al. ApoE4 accelerates early seeding of amyloid pathology. Neuron 2017; 96(5): 1024.e3-32.e3.
[http://dx.doi.org/10.1016/j.neuron.2017.11.013] [PMID: 29216449]
[152]
Ruiz C, Casarejos MJ, Gomez A, Solano R, de Yebenes JG, Mena MA. Protection by glia-conditioned medium in a cell model of Huntington disease. PLoS Curr 2012; 4: e4fbca54a2028b.
[http://dx.doi.org/10.1371/4fbca54a2028b]
[153]
Tanaka J, Toku K, Zhang B, Ishihara K, Sakanaka M, Maeda N. Astrocytes prevent neuronal death induced by reactive oxygen and nitrogen species. Glia 1999; 28(2): 85-96.
[http://dx.doi.org/10.1002/(SICI)1098-1136(199911)28:2<85:AID-GLIA1>3.0.CO;2-Y] [PMID: 10533053]
[154]
Oliveira AAB, Melo NFM, Vieira ÉS, et al. Palmitate treated-astrocyte conditioned medium contains increased glutathione and interferes in hypothalamic synaptic network in vitro. Neurochem Int 2018; 120: 140-8.
[http://dx.doi.org/10.1016/j.neuint.2018.08.010] [PMID: 30138641]
[155]
Asanuma M, Okumura-Torigoe N, Miyazaki I, Murakami S, Kitamura Y, Sendo T. Region-specific neuroprotective features of astrocytes against oxidative stress induced by 6-hydroxydopamine. Int J Mol Sci 2019; 20(3): 598.
[http://dx.doi.org/10.3390/ijms20030598] [PMID: 30704073]
[156]
Luo G, Huang Y, Jia B, et al. Quetiapine prevents Aβ25-35-induced cell death in cultured neuron by enhancing brain-derived neurotrophic factor release from astrocyte. Neuroreport 2018; 29(2): 92-8.
[http://dx.doi.org/10.1097/WNR.0000000000000911] [PMID: 29120942]
[157]
Wang K, Li H, Wang H, Wang J, Song F, Sun Y. Irisin exerts neuroprotective effects on cultured neurons by regulating astrocytes. Mediators Inflamm 2018; 2018: 1-7.
[http://dx.doi.org/10.1155/2018/9070341] [PMID: 30356412]
[158]
Durand D, Carniglia L, Turati J, et al. Amyloid-beta neurotoxicity and clearance are both regulated by glial group II metabotropic glutamate receptors. Neuropharmacology 2017; 123: 274-86.
[http://dx.doi.org/10.1016/j.neuropharm.2017.05.008] [PMID: 28495373]
[159]
Durand D, Carniglia L, Beauquis J, Caruso C, Saravia F, Lasaga M. Astroglial mGlu3 receptors promote alpha-secretase-mediated amyloid precursor protein cleavage. Neuropharmacology 2014; 79: 180-9.
[http://dx.doi.org/10.1016/j.neuropharm.2013.11.015] [PMID: 24291464]
[160]
Turati J, Rudi J, Beauquis J, et al. A metabotropic glutamate receptor 3 (mGlu3R) isoform playing neurodegenerative roles in astrocytes is prematurely up‐regulated in an Alzheimerʼs model. J Neurochem 2022; 161(4): 366-82.
[http://dx.doi.org/10.1111/jnc.15610] [PMID: 35411603]
[161]
Saba J, Turati J, Ramírez D, et al. Astrocyte truncated tropomyosin receptor kinase B mediates brain-derived neurotrophic factor anti-apoptotic effect leading to neuroprotection. J Neurochem 2018; 146(6): 686-702.
[http://dx.doi.org/10.1111/jnc.14476] [PMID: 29851427]
[162]
Gottschalk CG, Jana M, Roy A, Patel DR, Pahan K. Gemfibrozil protects dopaminergic neurons in a mouse model of parkinson’s disease via PPARα-dependent astrocytic GDNF pathway. J Neurosci 2021; 41(10): 2287-300.
[http://dx.doi.org/10.1523/JNEUROSCI.3018-19.2021] [PMID: 33514677]
[163]
Lin MS, Hung KS, Chiu WT, et al. Curcumin enhances neuronal survival in N-methyl-d-aspartic acid toxicity by inducing RANTES expression in astrocytes via PI-3K and MAPK signaling pathways. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35(4): 931-8.
[http://dx.doi.org/10.1016/j.pnpbp.2010.12.022] [PMID: 21199667]
[164]
Song C, Wu YS, Yang ZY, et al. Astrocyte-conditioned medium protects prefrontal cortical neurons from glutamate-induced cell death by inhibiting TNF-α expression. Neuroimmunomodulation 2019; 26(1): 33-42.
[http://dx.doi.org/10.1159/000495211] [PMID: 30699428]
[165]
Livne-Bar I, Wei J, Liu HH, et al. Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury. J Clin Invest 2017; 127(12): 4403-14.
[http://dx.doi.org/10.1172/JCI77398] [PMID: 29106385]
[166]
Gollihue JL, Norris CM. Astrocyte mitochondria: Central players and potential therapeutic targets for neurodegenerative diseases and injury. Ageing Res Rev 2020; 59: 101039.
[http://dx.doi.org/10.1016/j.arr.2020.101039] [PMID: 32105849]
[167]
Morales I, Sanchez A, Puertas-Avendaño R, Rodriguez-Sabate C, Perez-Barreto A, Rodriguez M. Neuroglial transmitophagy and Parkinson’s disease. Glia 2020; 68(11): 2277-99.
[http://dx.doi.org/10.1002/glia.23839] [PMID: 32415886]
[168]
Pickett EK, Rose J, McCrory C, et al. Region-specific depletion of synaptic mitochondria in the brains of patients with Alzheimer’s disease. Acta Neuropathol 2018; 136(5): 747-57.
[http://dx.doi.org/10.1007/s00401-018-1903-2] [PMID: 30191401]
[169]
Lampinen R, Belaya I, Saveleva L, et al. Neuron-astrocyte transmitophagy is altered in Alzheimer’s disease. Neurobiol Dis 2022; 170: 105753.
[http://dx.doi.org/10.1016/j.nbd.2022.105753] [PMID: 35569719]
[170]
Cheng XY, Biswas S, Li J, et al. Human iPSCs derived astrocytes rescue rotenone-induced mitochondrial dysfunction and dopaminergic neurodegeneration in vitro by donating functional mitochondria. Transl Neurodegener 2020; 9(1): 13.
[http://dx.doi.org/10.1186/s40035-020-00190-6] [PMID: 32345341]
[171]
Fontana IC, Souza DG, Souza DO, Gee A, Zimmer ER, Bongarzone S. A medicinal chemistry perspective on excitatory amino acid transporter 2 dysfunction in neurodegenerative diseases. J Med Chem 2023; 66(4): 2330-46.
[http://dx.doi.org/10.1021/acs.jmedchem.2c01572] [PMID: 36787643]
[172]
Fan S, Xian X, Li L, et al. Ceftriaxone improves cognitive function and upregulates GLT-1-related glutamate-glutamine cycle in APP/PS1 mice. J Alzheimers Dis 2018; 66(4): 1731-43.
[http://dx.doi.org/10.3233/JAD-180708] [PMID: 30452416]
[173]
Chotibut T, Meadows S, Kasanga EA, et al. Ceftriaxone reduces L -dopa-induced dyskinesia severity in 6-hydroxydopamine parkinson’s disease model. Mov Disord 2017; 32(11): 1547-56.
[http://dx.doi.org/10.1002/mds.27077] [PMID: 28631864]
[174]
Sari Y, Prieto AL, Barton SJ, Miller BR, Rebec GV. Ceftriaxone-induced up-regulation of cortical and striatal GLT1 in the R6/2 model of Huntington’s disease. J Biomed Sci 2010; 17(1): 62.
[http://dx.doi.org/10.1186/1423-0127-17-62] [PMID: 20663216]
[175]
Cudkowicz ME, Titus S, Kearney M, et al. Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: A multi-stage, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2014; 13(11): 1083-91.
[http://dx.doi.org/10.1016/S1474-4422(14)70222-4] [PMID: 25297012]
[176]
Martorana F, Brambilla L, Valori CF, et al. The BH4 domain of Bcl-XL rescues astrocyte degeneration in amyotrophic lateral sclerosis by modulating intracellular calcium signals. Hum Mol Genet 2012; 21(4): 826-40.
[http://dx.doi.org/10.1093/hmg/ddr513] [PMID: 22072391]
[177]
Vargas MR, Johnson DA, Sirkis DW, Messing A, Johnson JA. Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J Neurosci 2008; 28(50): 13574-81.
[http://dx.doi.org/10.1523/JNEUROSCI.4099-08.2008] [PMID: 19074031]
[178]
Vargas MR, Burton NC, Gan L, et al. Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models. PLoS One 2013; 8(2): e56625.
[http://dx.doi.org/10.1371/journal.pone.0056625] [PMID: 23418589]
[179]
Oksanen M, Hyötyläinen I, Trontti K, et al. NF‐E2‐related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin‐1 mutated Alzheimer’s disease astrocytes. Glia 2020; 68(3): 589-99.
[http://dx.doi.org/10.1002/glia.23741] [PMID: 31670864]
[180]
Jiwaji Z, Tiwari SS, Avilés-Reyes RX, et al. Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology. Nat Commun 2022; 13(1): 135.
[http://dx.doi.org/10.1038/s41467-021-27702-w] [PMID: 35013236]
[181]
Nakano-Kobayashi A, Canela A, Yoshihara T, Hagiwara M. Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway. Proc Natl Acad Sci 2023; 120(33): e2303809120.
[http://dx.doi.org/10.1073/pnas.2303809120] [PMID: 37549281]
[182]
Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol 2009; 27(1): 59-65.
[http://dx.doi.org/10.1038/nbt.1515] [PMID: 19098898]
[183]
Furman JL, Sama DM, Gant JC, et al. Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer’s disease. J Neurosci 2012; 32(46): 16129-40.
[http://dx.doi.org/10.1523/JNEUROSCI.2323-12.2012] [PMID: 23152597]
[184]
Fassler M, Weissberg I, Levy N, et al. Preferential lentiviral targeting of astrocytes in the central nervous system. PLoS One 2013; 8(10): e76092.
[http://dx.doi.org/10.1371/journal.pone.0076092] [PMID: 24098426]
[185]
Merienne N, Douce JL, Faivre E, Déglon N, Bonvento G. Efficient gene delivery and selective transduction of astrocytes in the mammalian brain using viral vectors. Front Cell Neurosci 2013; 7: 106.
[http://dx.doi.org/10.3389/fncel.2013.00106] [PMID: 23847471]
[186]
Humbel M, Ramosaj M, Zimmer V, et al. Maximizing lentiviral vector gene transfer in the CNS. Gene Ther 2021; 28(1-2): 75-88.
[http://dx.doi.org/10.1038/s41434-020-0172-6] [PMID: 32632267]
[187]
De Miranda BR, Rocha EM, Bai Q, et al. Astrocyte-specific DJ-1 overexpression protects against rotenone-induced neurotoxicity in a rat model of Parkinson’s disease. Neurobiol Dis 2018; 115: 101-14.
[http://dx.doi.org/10.1016/j.nbd.2018.04.008] [PMID: 29649621]
[188]
Revilla S, Ursulet S, Álvarez-López MJ, et al. Lenti-GDNF gene therapy protects against Alzheimer’s disease-like neuropathology in 3xTg-AD mice and MC65 cells. CNS Neurosci Ther 2014; 20(11): 961-72.
[http://dx.doi.org/10.1111/cns.12312] [PMID: 25119316]
[189]
Lee YF, Russ AN, Zhao Q, et al. Optogenetic targeting of astrocytes restores slow brain rhythm function and slows alzheimer’s disease pathology. Res Sq 2023; 3: 2813056.
[190]
Hohnholt MC, Geppert M, Luther EM, Petters C, Bulcke F, Dringen R. Handling of iron oxide and silver nanoparticles by astrocytes. Neurochem Res 2013; 38(2): 227-39.
[http://dx.doi.org/10.1007/s11064-012-0930-y] [PMID: 23224777]
[191]
Chang X, Li J, Niu S, Xue Y, Tang M. Neurotoxicity of metal‐containing nanoparticles and implications in glial cells. J Appl Toxicol 2021; 41(1): 65-81.
[http://dx.doi.org/10.1002/jat.4037] [PMID: 32686875]
[192]
Tanaka H, Nakatani T, Furihata T, et al. In vivo introduction of mrna encapsulated in lipid nanoparticles to brain neuronal cells and astrocytes via intracerebroventricular administration. Mol Pharm 2018; 15(5): 2060-7.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b01084] [PMID: 29638135]
[193]
El-Mezayen NS, Attia MAM, Shafik MY, et al. Reactive astrocytes targeting with oral vitamin A: Efficient neuronal regeneration for Parkinson’s disease treatment and reversal of associated liver fibrosis. CNS Neurosci Ther 2023; 29(8): 2111-28.
[http://dx.doi.org/10.1111/cns.14179] [PMID: 36949616]
[194]
Söllvander S, Nikitidou E, Brolin R, et al. Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol Neurodegener 2016; 11(1): 38.
[http://dx.doi.org/10.1186/s13024-016-0098-z] [PMID: 27176225]
[195]
Nikitidou E, Khoonsari PE, Shevchenko G, Ingelsson M, Kultima K, Erlandsson A. Increased release of apolipoprotein E in extracellular vesicles following amyloid-β protofibril exposure of neuroglial co-cultures. J Alzheimers Dis 2017; 60(1): 305-21.
[http://dx.doi.org/10.3233/JAD-170278] [PMID: 28826183]
[196]
Goetzl EJ, Schwartz JB, Abner EL, Jicha GA, Kapogiannis D. High complement levels in astrocyte-derived exosomes of Alzheimer disease. Ann Neurol 2018; 83(3): 544-52.
[http://dx.doi.org/10.1002/ana.25172] [PMID: 29406582]
[197]
Winston CN, Goetzl EJ, Schwartz JB, Elahi FM, Rissman RA. Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer’s disease dementia. Alzheimers Dement 2019; 11(1): 61-6.
[http://dx.doi.org/10.1016/j.dadm.2018.11.002] [PMID: 31032394]
[198]
Emmanouilidou E, Melachroinou K, Roumeliotis T, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 2010; 30(20): 6838-51.
[http://dx.doi.org/10.1523/JNEUROSCI.5699-09.2010] [PMID: 20484626]
[199]
Hong Y, Zhao T, Li XJ, Li S. Mutant huntingtin inhibits αB-crystallin expression and impairs exosome secretion from astrocytes. J Neurosci 2017; 37(39): 9550-63.
[http://dx.doi.org/10.1523/JNEUROSCI.1418-17.2017] [PMID: 28893927]
[200]
Basso M, Pozzi S, Tortarolo M, et al. Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: Implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis. J Biol Chem 2013; 288(22): 15699-711.
[http://dx.doi.org/10.1074/jbc.M112.425066] [PMID: 23592792]
[201]
Chen Y, Xia K, Chen L, Fan D. Increased interleukin-6 levels in the astrocyte-derived exosomes of sporadic amyotrophic lateral sclerosis patients. Front Neurosci 2019; 13: 574.
[http://dx.doi.org/10.3389/fnins.2019.00574] [PMID: 31231184]
[202]
Nafar F, Williams JB, Mearow KM. Astrocytes release HspB1 in response to amyloid-β exposure in vitro. J Alzheimers Dis 2015; 49(1): 251-63.
[http://dx.doi.org/10.3233/JAD-150317] [PMID: 26444769]
[203]
Peng D, Wang Y, Xiao Y, et al. Extracellular vesicles derived from astrocyte-treated with haFGF14-154 attenuate Alzheimer phenotype in AD mice. Theranostics 2022; 12(8): 3862-81.
[http://dx.doi.org/10.7150/thno.70951] [PMID: 35664060]
[204]
Venturini A, Passalacqua M, Pelassa S, et al. Exosomes from astrocyte processes: Signaling to neurons. Front Pharmacol 2019; 10: 1452.
[http://dx.doi.org/10.3389/fphar.2019.01452] [PMID: 31849688]
[205]
Muhammad SA. Are extracellular vesicles new hope in clinical drug delivery for neurological disorders? Neurochem Int 2021; 144: 104955.
[http://dx.doi.org/10.1016/j.neuint.2021.104955] [PMID: 33412233]
[206]
Hart CG, Karimi-Abdolrezaee S. Recent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair. J Neurosci Res 2021; 99(10): 2427-62.
[http://dx.doi.org/10.1002/jnr.24922] [PMID: 34259342]
[207]
Proschel C, Stripay JL, Shih CH, Munger JC, Noble MD. Delayed transplantation of precursor cell‐derived astrocytes provides multiple benefits in a rat model of P arkinsons. EMBO Mol Med 2014; 6(4): 504-18.
[http://dx.doi.org/10.1002/emmm.201302878] [PMID: 24477866]
[208]
Lepore AC, Rauck B, Dejea C, et al. Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat Neurosci 2008; 11(11): 1294-301.
[http://dx.doi.org/10.1038/nn.2210] [PMID: 18931666]
[209]
Kondo T, Funayama M, Tsukita K, et al. Focal transplantation of human iPSC-derived glial-rich neural progenitors improves lifespan of ALS mice. Stem Cell Reports 2014; 3(2): 242-9.
[http://dx.doi.org/10.1016/j.stemcr.2014.05.017] [PMID: 25254338]
[210]
Baloh RH, Johnson JP, Avalos P, et al. Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: A phase 1/2a trial. Nat Med 2022; 28(9): 1813-22.
[http://dx.doi.org/10.1038/s41591-022-01956-3] [PMID: 36064599]
[211]
Wu Z, Parry M, Hou XY, et al. Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington’s disease. Nat Commun 2020; 11(1): 1105.
[http://dx.doi.org/10.1038/s41467-020-14855-3] [PMID: 32107381]
[212]
Qian H, Kang X, Hu J, et al. Reversing a model of Parkinson’s disease with in situ converted nigral neurons. Nature 2020; 582(7813): 550-6.
[http://dx.doi.org/10.1038/s41586-020-2388-4] [PMID: 32581380]
[213]
Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model. Cell Stem Cell 2014; 14(2): 188-202.
[http://dx.doi.org/10.1016/j.stem.2013.12.001] [PMID: 24360883]
[214]
Wang LL, Serrano C, Zhong X, Ma S, Zou Y, Zhang CL. Revisiting astrocyte to neuron conversion with lineage tracing in vivo. Cell 2021; 184(21): 5465-5481.e16.
[http://dx.doi.org/10.1016/j.cell.2021.09.005] [PMID: 34582787]
[215]
Wang Q, Li W, Lei W, et al. Lineage tracing of direct astrocyte-to-neuron conversion in the mouse cortex. Neural Regen Res 2021; 16(4): 750-6.
[http://dx.doi.org/10.4103/1673-5374.295925] [PMID: 33063738]

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