{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:04:16Z","timestamp":1792796656925,"version":"4.5.0"},"reference-count":259,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>In a healthy physiological context, astrocytes are multitasking cells contributing to central nervous system (CNS) homeostasis, defense, and immunity. In cell culture or rodent models of age-related neurodegenerative diseases (NDDs), such as Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD), numerous studies have shown that astrocytes can adopt neurotoxic phenotypes that could enhance disease progression. Chronic inflammatory responses, oxidative stress, unbalanced phagocytosis, or alteration of their core physiological roles are the main manifestations of their detrimental states. However, if astrocytes are directly involved in brain deterioration by exerting neurotoxic functions in patients with NDDs is still controversial. The large spectrum of NDDs, with often overlapping pathologies, and the technical challenges associated with the study of human brain samples complexify the analysis of astrocyte involvement in specific neurodegenerative cascades. With this review, we aim to provide a translational overview about the multi-facets of astrocyte neurotoxicity ranging from <jats:italic>in vitro<\/jats:italic> findings over mouse and human cell-based studies to rodent NDDs research and finally evidence from patient-related research. We also discuss the role of ageing in astrocytes encompassing changes in physiology and response to pathologic stimuli and how this may prime detrimental responses in NDDs. To conclude, we discuss how potentially therapeutic strategies could be adopted to alleviate or reverse astrocytic toxicity and their potential to impact neurodegeneration and dementia progression in patients.<\/jats:p>","DOI":"10.3389\/fphys.2022.814889","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T12:50:19Z","timestamp":1647521419000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["The Multifaceted Neurotoxicity of Astrocytes in Ageing and Age-Related Neurodegenerative Diseases: A Translational Perspective"],"prefix":"10.3389","volume":"13","author":[{"given":"David S.","family":"Bouvier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Fixemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Heurtaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9licia","family":"Jeannelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin B. M.","family":"Frauenknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Mittelbronn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1192\/bjp.135.3.216","article-title":"Changes in the brain catecholamines in patients with dementia of Alzheimer type","volume":"135","author":"Adolfsson","year":"1979","journal-title":"Br. J. Psychiatry"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"4183","DOI":"10.1038\/s41467-020-17876-0","article-title":"A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders","volume":"11","author":"Agarwal","year":"2020","journal-title":"Nat. Commun."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"5795","DOI":"10.1073\/pnas.95.10.5795","article-title":"Amyloid \u03b2-peptide stimulates nitric oxide production in astrocytes through an NF\u03bab-dependent mechanism","volume":"95","author":"Akama","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.neuron.2017.09.056","article-title":"Cell biology of astrocyte-synapse interactions","volume":"96","author":"Allen","year":"2017","journal-title":"Neuron"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1002\/glia.22989","article-title":"Connexin 43 in astrocytes contributes to motor neuron toxicity in amyotrophic lateral sclerosis","volume":"64","author":"Almad","year":"2016","journal-title":"Glia"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/(SICI)1097-0029(19981001)43:1<29::AID-JEMT5>3.0.CO;2-H","article-title":"Astrocyte changes in cerebral cortex and hippocampus: A quantitative immunohistochemical study","volume":"43","author":"Amenta","year":"1998","journal-title":"Microsc. Res. Tech."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.neuron.2014.02.007","article-title":"Gliotransmitters travel in time and space","volume":"81","author":"Araque","year":"2014","journal-title":"Neuron"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1755-7682-3-24","article-title":"Dopaminergic reward system: a short integrative review","volume":"3","author":"Arias-Carri\u00e1n","year":"2010","journal-title":"Int. Arch. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/nature16932","article-title":"Naturally occurring p16 Ink4a-positive cells shorten healthy lifespan","volume":"530","author":"Baker","year":"2016","journal-title":"Nature"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"104511","DOI":"10.1016\/j.nbd.2019.104511","article-title":"Neurotoxic astrocytes express the D-serine synthesizing enzyme, serine racemase, in Alzheimer\u2019s disease","volume":"130","author":"Balu","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3389\/fnana.2018.00044","article-title":"Adult hippocampal neurogenesis: regulation and possible functional and clinical correlates","volume":"12","author":"Baptista","year":"2018","journal-title":"Front. Neuroanat."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3390\/ijms17030338","article-title":"Amyloid-\u03b2 and astrocytes interplay in amyloid-\u03b2 related disorders","volume":"17","author":"Batarseh","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1038\/s41467-019-14198-8","article-title":"Identification of region-specific astrocyte subtypes at single cell resolution","volume":"11","author":"Batiuk","year":"2020","journal-title":"Nat. Commun."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3233\/JAD-210191","article-title":"The locus coeruleus in aging and Alzheimer\u2019s disease: a postmortem and brain imaging review","volume":"83","author":"Beardmore","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1126\/science.1203295","article-title":"Behavior and the dynamic genome","volume":"332","author":"Bell","year":"2011","journal-title":"Science"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1111\/j.1474-9726.2011.00694.x","article-title":"Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells","volume":"10","author":"Bernal","year":"2011","journal-title":"Aging Cell"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e45069","DOI":"10.1371\/journal.pone.0045069","article-title":"Astrocyte senescence as a component of Alzheimer\u2019s disease","volume":"7","author":"Bhat","year":"2012","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"4069","DOI":"10.1073\/pnas.1218497110","article-title":"Reactive astrocytes secrete lcn2 to promote neuron death","volume":"110","author":"Bi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3114","DOI":"10.1093\/brain\/awab191","article-title":"The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson\u2019s disease","volume":"144","author":"Biondetti","year":"2021","journal-title":"Brain"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1101\/gad.343129.120","article-title":"Senescence and the SASP: many therapeutic avenues","volume":"34","author":"Birch","year":"2020","journal-title":"Genes Dev."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.ebiom.2019.11.026","article-title":"Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity","volume":"50","author":"Birger","year":"2019","journal-title":"EBioMedicine"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.1016\/j.yexcr.2010.06.021","article-title":"Stress-induced senescence in human and rodent astrocytes","volume":"316","author":"Bitto","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.tins.2007.03.006","article-title":"Dopamine neuron systems in the brain: an update","volume":"30","author":"Bj\u00f6rklund","year":"2007","journal-title":"Trends Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.celrep.2017.12.039","article-title":"The aging astrocyte transcriptome from multiple regions of the mouse brain","volume":"22","author":"Boisvert","year":"2018","journal-title":"Cell Rep."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.stem.2018.03.015","article-title":"Human hippocampal neurogenesis persists throughout aging","volume":"22","author":"Boldrini","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.celrep.2018.06.044","article-title":"Neuron-astroglia cell fate decision in the adult mouse hippocampal neurogenic niche is cell-intrinsically controlled by COUP-TFI in vivo","volume":"24","author":"Bonzano","year":"2018","journal-title":"Cell Rep."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"24544","DOI":"10.1038\/srep24544","article-title":"High resolution dissection of reactive glial nets in Alzheimer\u2019s disease","volume":"6","author":"Bouvier","year":"2016","journal-title":"Sci. Rep."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.3233\/JAD-143156","article-title":"Synergistic actions of microglia and astrocytes in the progression of Alzheimer\u2019s disease","volume":"45","author":"Bouvier","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e12914","DOI":"10.1111\/bpa.12914","article-title":"Contribution of the astrocytic tau pathology to synapse loss in progressive supranuclear palsy and corticobasal degeneration","volume":"31","author":"Briel","year":"2021","journal-title":"Brain Pathol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"644","DOI":"10.3389\/fphar.2019.00644","article-title":"Astrocyte function is affected by aging and not Alzheimer\u2019s disease: a preliminary investigation in hippocampi of 3xTg-AD mice","volume":"10","author":"Bronzuoli","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.pharmthera.2015.11.003","article-title":"Nrf2-ARE pathway: an emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases","volume":"157","author":"Buendia","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.ijdevneu.2003.12.008","article-title":"Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development","volume":"22","author":"Bushong","year":"2004","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1523\/JNEUROSCI.22-01-00183.2002","article-title":"Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains","volume":"22","author":"Bushong","year":"2002","journal-title":"J. Neurosci."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/s41586-018-0543-y","article-title":"Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline","volume":"562","author":"Bussian","year":"2018","journal-title":"Nature"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3389\/fncel.2014.00152","article-title":"Microglia change from a reactive to an age-like phenotype with the time in culture","volume":"8","author":"Caldeira","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"5848","DOI":"10.1038\/s41380-021-01193-z","article-title":"Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load","volume":"26","author":"Calsolaro","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"388","DOI":"10.2174\/187152707783399193","article-title":"Microglia-neuron interaction in inflammatory and degenerative diseases: role of cholinergic and noradrenergic systems","volume":"6","author":"Carnevale","year":"2007","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.molmed.2018.11.006","article-title":"Astrocyte biomarkers in Alzheimer\u2019s disease","volume":"25","author":"Carter","year":"2019","journal-title":"Trends Mol. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2967\/jnumed.110.087031","article-title":"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","volume":"53","author":"Carter","year":"2012","journal-title":"J. Nucl. Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e45250","DOI":"10.1371\/journal.pone.0045250","article-title":"The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus","volume":"7","author":"Cerbai","year":"2012","journal-title":"PLoS One"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s40478-018-0606-1","article-title":"Modulation of astrocyte reactivity improves functional deficits in mouse models of Alzheimer\u2019s disease","volume":"6","author":"Ceyz\u00e9riat","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/alzrt175","article-title":"Targeting norepinephrine in mild cognitive impairment and Alzheimer\u2019s disease","volume":"5","author":"Chalermpalanupap","year":"2013","journal-title":"Alzheimers Res. Ther."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41398-020-01137-1","article-title":"Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer\u2019s disease","volume":"11","author":"Chatterjee","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"3153","DOI":"10.1042\/BCJ20180297","article-title":"Impact of monomeric, oligomeric and fibrillar alpha-synuclein on astrocyte reactivity and toxicity to neurons","volume":"475","author":"Chavarr\u00eda","year":"2018","journal-title":"Biochem. J."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/sj.mp.4001893","article-title":"Valproate protects dopaminergic neurons in midbrain neuron\/glia cultures by stimulating the release of neurotrophic factors from astrocytes","volume":"11","author":"Chen","year":"2006","journal-title":"Mol. Psychiatry"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.celrep.2017.12.092","article-title":"Cellular senescence is induced by the environmental neurotoxin paraquat and contributes to neuropathology linked to parkinson\u2019s disease","volume":"22","author":"Chinta","year":"2018","journal-title":"Cell Rep."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1080\/15592294.2014.1001219","article-title":"Histone methylation patterns in astrocytes are influenced by age following ischemia","volume":"10","author":"Chisholm","year":"2015","journal-title":"Epigenetics"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/s41419-021-04049-0","article-title":"Fibrillar \u03b1-synuclein induces neurotoxic astrocyte activation via RIP kinase signaling and NF-\u03baB","volume":"12","author":"Chou","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.cell.2004.12.020","article-title":"Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis","volume":"120","author":"Christopherson","year":"2005","journal-title":"Cell"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1038\/s41593-020-00735-y","article-title":"Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer\u2019s disease via H2O2\u2212 production","volume":"23","author":"Chun","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/nature12776","article-title":"Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways","volume":"504","author":"Chung","year":"2013","journal-title":"Nature"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13024-021-00476-x","article-title":"Cellular and pathological heterogeneity of primary tauopathies","volume":"16","author":"Chung","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13195-021-00804-9","article-title":"Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment","volume":"13","author":"Cicognola","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"E1896","DOI":"10.1073\/pnas.1800165115","article-title":"Normal aging induces A1-like astrocyte reactivity","volume":"115","author":"Clarke","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/jnen\/64.2.163","article-title":"Proliferative potential of human astrocytes","volume":"64","author":"Colodner","year":"2005","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/neuroglia1010003","article-title":"Interlaminar glia and other glial themes revisited: pending answers following three decades of glial research","volume":"1","author":"Colombo","year":"2018","journal-title":"Neuroglia"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"220","DOI":"10.3389\/fgene.2014.00220","article-title":"The potential of epigenetic therapies in neurodegenerative diseases","volume":"5","author":"Copped\u00e8","year":"2014","journal-title":"Front. Genet."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1016\/j.neurobiolaging.2013.11.031","article-title":"Global changes in DNA methylation and hydroxymethylation in Alzheimer\u2019s disease human brain","volume":"35","author":"Coppieters","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.neuron.2019.12.026","article-title":"Dopamine-evoked synaptic regulation in the nucleus accumbens requires astrocyte activity","volume":"105","author":"Corkrum","year":"2020","journal-title":"Neuron"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3389\/fnagi.2016.00208","article-title":"Changes in the transcriptome of human astrocytes accompanying oxidative stress-induced senescence","volume":"8","author":"Crowe","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/jbt.21803","article-title":"Ferrous iron induces Nrf2 expression in mouse brain astrocytes to prevent neurotoxicity","volume":"30","author":"Cui","year":"2016","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"6089","DOI":"10.18632\/aging.103008","article-title":"Estradiol-induced senescence of hypothalamic astrocytes contributes to aging-related reproductive function declines in female mice","volume":"12","author":"Dai","year":"2020","journal-title":"Aging"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/S0304-3940(97)00708-8","article-title":"Glial reaction in the hippocampal formation is highly correlated with aging in human brain","volume":"235","author":"David","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/alz.047419","article-title":"Ablation of astrocytes affects A\u03b2 degradation, microglia activation and synaptic connectivity in an ex vivo model of Alzheimer\u2019s disease","volume":"16","author":"Davis","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.cell.2015.12.056","article-title":"The cellular phase of Alzheimer\u2019s disease","volume":"164","author":"De Strooper","year":"2016","journal-title":"Cell"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"246","DOI":"10.3389\/fncel.2015.00246","article-title":"Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function","volume":"9","author":"De Zeeuw","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.3389\/fnins.2019.01301","article-title":"Energy dynamics in the brain: contributions of astrocytes to metabolism and pH homeostasis","volume":"13","author":"Deitmer","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1002\/glia.23728","article-title":"The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins","volume":"68","author":"Deora","year":"2020","journal-title":"Glia"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41580-020-00314-w","article-title":"Cellular senescence in ageing: from mechanisms to therapeutic opportunities","volume":"22","author":"Di Micco","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.ceca.2013.09.001","article-title":"\u03b11-adrenergic receptors mediate coordinated Ca2+ signaling of cortical astrocytes in awake, behaving mice","volume":"54","author":"Ding","year":"2013","journal-title":"Cell Calcium"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive astrocyte nomenclature, definitions, and future directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/glia.10301","article-title":"Progressive telomere shortening occurs in cultured rat microglia, but not astrocytes","volume":"45","author":"Flanary","year":"2004","journal-title":"Glia"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1742-2094-8-4","article-title":"Contribution of complement activation pathways to neuropathology differs among mouse models of Alzheimer\u2019s disease","volume":"8","author":"Fonseca","year":"2011","journal-title":"J. Neuroinflammation"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"3539","DOI":"10.1523\/JNEUROSCI.0081-05.2005","article-title":"Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration","volume":"25","author":"Forman","year":"2005","journal-title":"J. Neurosci."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3233\/JAD-2009-1134","article-title":"Dysregulation of histone acetylation in the APP\/PS1 mouse model of Alzheimer\u2019s disease","volume":"18","author":"Francis","year":"2009","journal-title":"J. Alzheimers Dis."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"170228","DOI":"10.1098\/rsob.170228","article-title":"The role of astrocytes in amyloid production and Alzheimer\u2019s disease","volume":"7","author":"Frost","year":"2017","journal-title":"Open Biol."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"e1005582","DOI":"10.1371\/journal.pgen.1005582","article-title":"A role for the chaperone complex BAG3-HSPB8 in actin dynamics, spindle orientation and proper chromosome segregation during mitosis","volume":"11","author":"Fuchs","year":"2015","journal-title":"PLoS Genet."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1042\/BJ20090907","article-title":"Identification of the key structural motifs involved in HspB8\/HspB6-Bag3 interaction","volume":"425","author":"Fuchs","year":"2010","journal-title":"Biochem. J."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"16129","DOI":"10.1523\/JNEUROSCI.2323-12.2012","article-title":"Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer\u2019s disease","volume":"32","author":"Furman","year":"2012","journal-title":"J. Neurosci."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"109419","DOI":"10.1016\/j.celrep.2021.109419","article-title":"Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer\u2019s disease and frontotemporal dementia","volume":"36","author":"Gaikwad","year":"2021","journal-title":"Cell Rep."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"4846","DOI":"10.1523\/JNEUROSCI.3349-17.2018","article-title":"Dopamine triggers CTCF-dependent morphological and genomic remodeling of astrocytes","volume":"38","author":"Galloway","year":"2018","journal-title":"J. Neurosci."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"8526","DOI":"10.1073\/pnas.1605063113","article-title":"Astrocytic \u03b22-adrenergic receptors mediate hippocampal long-term memory consolidation","volume":"113","author":"Gao","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/cddis.2011.50","article-title":"Astrocytes are important mediators of A\u03b2-induced neurotoxicity and tau phosphorylation in primary culture","volume":"2","author":"Garwood","year":"2011","journal-title":"Cell Death Dis."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"P1257","DOI":"10.1016\/j.jalz.2019.06.4793","article-title":"O4-09-06: clonally expanded Cd8 T cells patrol Alzheimer\u2019s cerebrospinal fluid","volume":"15","author":"Gate","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"18923","DOI":"10.1038\/s41598-020-75014-8","article-title":"Genealogy of the neurodegenerative diseases based on a meta-analysis of age-stratified incidence data","volume":"10","author":"Gerovska","year":"2020","journal-title":"Sci. Rep."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s00401-021-02263-w","article-title":"Distinct amyloid-\u03b2 and tau-associated microglia profiles in Alzheimer\u2019s disease","volume":"141","author":"Gerrits","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/hdy.2010.54","article-title":"Epigenetics and gene expression","volume":"105","author":"Gibney","year":"2010","journal-title":"Heredity"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1002\/ana.25172","article-title":"High complement levels in astrocyte-derived exosomes of Alzheimer disease","volume":"83","author":"Goetzl","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1172\/JCI66029","article-title":"Thinking laterally about neurodegenerative proteinopathies","volume":"123","author":"Golde","year":"2013","journal-title":"J. Clin. Invest."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1111\/nan.12525","article-title":"Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes","volume":"45","author":"Gorter","year":"2019","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1038\/s41593-019-0539-4","article-title":"A single-cell atlas of entorhinal cortex from individuals with Alzheimer\u2019s disease reveals cell-type-specific gene expression regulation","volume":"22","author":"Grubman","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1756-6606-3-12","article-title":"Astrocytic expression of Parkinson\u2019s disease-related A53T-synuclein causes neurodegeneration in mice","volume":"3","author":"Gu","year":"2010","journal-title":"Mol. Brain"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3389\/fncel.2017.00427","article-title":"Functional roles of astrocyte calcium elevations: From synapses to behavior","volume":"11","author":"Guerra-Gomes","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41593-020-00796-z","article-title":"Fully defined human pluripotent stem cell-derived microglia and tri-culture system model C3 production in Alzheimer\u2019s disease","volume":"24","author":"Guttikonda","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41593-020-0624-8","article-title":"Disease-associated astrocytes in Alzheimer\u2019s disease and aging","volume":"23","author":"Habib","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/nbt.1957","article-title":"Astrocytes from familial and sporadic ALS patients are toxic to motor neurons","volume":"29","author":"Haidet-Phillips","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1523\/JNEUROSCI.3516-14.2015","article-title":"The JAK\/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer\u2019s and Huntington\u2019s diseases","volume":"35","author":"Haim","year":"2015","journal-title":"J. Neurosci."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"2727602","DOI":"10.1155\/2017\/2727602","article-title":"The longevity of hippocampus-dependent memory is orchestrated by the locus Coeruleus-noradrenergic system","volume":"2017","author":"Hansen","year":"2017","journal-title":"Neural Plast."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/s41593-021-00905-6","article-title":"Neuroinflammatory astrocyte subtypes in the mouse brain","volume":"24","author":"Hasel","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref101","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/978-3-319-16077-1_6","article-title":"Regulation of the chaperone function of small Hsps","volume-title":"The Big Book on Small Heat Shock Proteins","author":"Haslbeck","year":"2015"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"e3189","DOI":"10.1371\/journal.pone.0003189","article-title":"Astrocyte-specific genes are generally demethylated in neural precursor cells prior to astrocytic differentiation","volume":"3","author":"Hatada","year":"2008","journal-title":"PLoS One"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41577-018-0112-5","article-title":"Microglia take Centre stage in neurodegenerative disease","volume":"19","author":"Heneka","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1523\/JNEUROSCI.22-07-02434.2002","article-title":"Noradrenergic depletion potentiates \u03b2-amyloid-induced cortical inflammation: implications for Alzheimer\u2019s disease","volume":"22","author":"Heneka","year":"2002","journal-title":"J. Neurosci."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.1073\/pnas.0909586107","article-title":"Locus ceruleus controls Alzheimer\u2019s disease pathology by modulating microglial functions through norepinephrine","volume":"107","author":"Heneka","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1523\/JNEUROSCI.4236-05.2006","article-title":"Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice","volume":"26","author":"Heneka","year":"2006","journal-title":"J. Neurosci."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1742-2094-2-22","article-title":"Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice","volume":"2","author":"Heneka","year":"2005","journal-title":"J. Neuroinflammation"},{"key":"ref108","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1093\/jnen\/60.9.906","article-title":"Neuronal and glial coexpression of argininosuccinate synthetase and inducible nitric oxide synthase in Alzheimer disease","volume":"60","author":"Heneka","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref109","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01131-1","article-title":"Apomorphine reduces A53T \u03b1-synuclein-induced microglial reactivity through activation of NRF2 signalling pathway","author":"Heurtaux","year":"2021","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s00401-004-0967-3","article-title":"Tuft-shaped astrocytes in Lewy body disease","volume":"109","author":"Hishikawa","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1093\/brain\/awab111","article-title":"The role of noradrenaline in cognition and cognitive disorders","volume":"144","author":"Holland","year":"2021","journal-title":"Brain"},{"key":"ref112","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1111\/jnc.12660","article-title":"Profiling the genes affected by pathogenic TDP-43 in astrocytes","volume":"129","author":"Huang","year":"2014","journal-title":"J. Neurochem."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"657514","DOI":"10.3389\/fnmol.2021.657514","article-title":"Astroglial connexins in neurodegenerative diseases","volume":"14","author":"Huang","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.neuroscience.2021.03.023","article-title":"Expression and cell type-specific localization of Inflammasome sensors in the spinal cord of SOD1(G93A) mice and sporadic amyotrophic lateral sclerosis patients","volume":"463","author":"Hummel","year":"2021","journal-title":"Neuroscience"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"135972","DOI":"10.1016\/j.neulet.2021.135972","article-title":"The stimulator of interferon genes (STING) pathway is upregulated in striatal astrocytes of patients with multiple system atrophy","volume":"757","author":"Inoue","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"824","DOI":"10.3389\/fnins.2020.00824","article-title":"Rising stars: astrocytes as a therapeutic target for ALS disease","volume":"14","author":"Izrael","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/s41586-019-0903-2","article-title":"Altered human oligodendrocyte heterogeneity in multiple sclerosis","volume":"566","author":"J\u00e4kel","year":"2019","journal-title":"Nature"},{"key":"ref118","doi-asserted-by":"publisher","first-page":"15604","DOI":"10.1073\/pnas.0902177106","article-title":"Substrate binding site flexibility of the small heat shock protein molecular chaperones","volume":"106","author":"Jaya","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"2260","DOI":"10.1002\/glia.22891","article-title":"NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients","volume":"63","author":"Johann","year":"2015","journal-title":"Glia"},{"key":"ref120","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1196\/annals.1427.036","article-title":"The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration","volume":"1147","author":"Johnson","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref121","doi-asserted-by":"publisher","first-page":"321209","DOI":"10.1155\/2014\/321209","article-title":"Astrocyte-secreted matricellular proteins in CNS remodelling during development and disease","volume":"2014","author":"Jones","year":"2014","journal-title":"Neural Plast."},{"key":"ref122","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1038\/s41593-019-0486-0","article-title":"Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration","volume":"22","author":"Joshi","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1016\/j.neurobiolaging.2006.06.003","article-title":"Noradrenaline deficiency in brain increases \u03b2-amyloid plaque burden in an animal model of Alzheimer\u2019s disease","volume":"28","author":"Kalinin","year":"2007","journal-title":"Neurobiol. Aging"},{"key":"ref124","doi-asserted-by":"publisher","first-page":"577744","DOI":"10.1016\/j.jneuroim.2021.577744","article-title":"Salivary GFAP as a potential biomarker for diagnosis of mild cognitive impairment and Alzheimer\u2019s disease and its correlation with neuroinflammation and apoptosis","volume":"361","author":"Katsipis","year":"2021","journal-title":"J. Neuroimmunol."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1002\/glia.23759","article-title":"Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer\u2019s disease","volume":"68","author":"Katsouri","year":"2020","journal-title":"Glia"},{"key":"ref126","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1046\/j.1440-1789.2003.00483.x","article-title":"Immunohistochemical study of the expression of cytokines and nitric oxide synthases in brains of patients with dementia with Lewy bodies","volume":"23","author":"Katsuse","year":"2003","journal-title":"Neuropathology"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1111\/neup.12716","article-title":"Astrocytes release glutamate via cystine\/glutamate antiporter upregulated in response to increased oxidative stress related to sporadic amyotrophic lateral sclerosis","volume":"40","author":"Kazama","year":"2020","journal-title":"Neuropathology"},{"key":"ref128","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1073\/pnas.98.4.1964","article-title":"An astroglia-linked dopamine D2-receptor action in prefrontal cortex","volume":"98","author":"Khan","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1002\/glia.23298","article-title":"Astrocytes expressing ALS-linked mutant FUS induce motor neuron death through release of tumor necrosis factor-alpha","volume":"66","author":"Kia","year":"2018","journal-title":"Glia"},{"key":"ref130","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.2174\/1568026615666141208105614","article-title":"An overview of naturally occurring histone deacetylase inhibitors","volume":"14","author":"Kim","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3390\/brainsci10080503","article-title":"The increased densities, but different distributions, of both C3 and S100A10 immunopositive astrocyte-like cells in alzheimer\u2019s disease brains suggest possible roles for both A1 and A2 astrocytes in the disease pathogenesis","volume":"10","author":"King","year":"2020","journal-title":"Brain Sci."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1038\/s41598-018-19442-7","article-title":"Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain","volume":"8","author":"Kobayashi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.vascn.2012.08.001","article-title":"Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders","volume":"66","author":"Konsoula","year":"2012","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref134","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00401-015-1509-x","article-title":"Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy","volume":"131","author":"Kovacs","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref135","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s40478-018-0552-y","article-title":"Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain","volume":"6","author":"Kovacs","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref136","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1096\/fj.12-208660","article-title":"Attenuating astrocyte activation accelerates plaque pathogenesis in APP\/PS1 mice","volume":"27","author":"Kraft","year":"2013","journal-title":"FASEB J."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"E4530","DOI":"10.1073\/pnas.1318835110","article-title":"Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration","volume":"110","author":"Lagier-Tourenne","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1038\/nbt.4038","article-title":"Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain","volume":"36","author":"Lake","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref140","doi-asserted-by":"publisher","first-page":"25800","DOI":"10.1073\/pnas.2008762117","article-title":"Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer\u2019s disease","volume":"117","author":"Lau","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref141","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-020-01963-6","article-title":"The overexpression of TDP-43 in astrocytes causes neurodegeneration via a PTP1B-mediated inflammatory response","volume":"17","author":"Lee","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref142","doi-asserted-by":"publisher","first-page":"3958","DOI":"10.1038\/s41467-021-24232-3","article-title":"Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1523\/JNEUROSCI.2117-15.2016","article-title":"Astrocyte-microglia cross talk through complement activation modulates amyloid pathology in mouse models of alzheimer\u2019s disease","volume":"36","author":"Lian","year":"2016","journal-title":"J. Neurosci."},{"key":"ref144","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref145","doi-asserted-by":"publisher","first-page":"e0227887","DOI":"10.1371\/journal.pone.0227887","article-title":"Astrocyte senescence promotes glutamate toxicity in cortical neurons","volume":"15","author":"Limbad","year":"2020","journal-title":"PLoS One"},{"key":"ref146","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3390\/cells8030271","article-title":"Lamina associated domains and gene regulation in development and cancer","volume":"8","author":"Lochs","year":"2019","journal-title":"Cell"},{"key":"ref147","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1007\/s12031-011-9636-x","article-title":"Clinical phenomenology and neuroimaging correlates in ALS-FTD","volume":"45","author":"Lomen-Hoerth","year":"2011","journal-title":"J. Mol. Neurosci."},{"key":"ref148","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1080\/00207450601059429","article-title":"H2O2-induced changes in astrocytic cultures from control and rapidly aging strains of mouse","volume":"118","author":"L\u00fc","year":"2008","journal-title":"Int. J. Neurosci."},{"key":"ref149","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0006-8993(02)03280-8","article-title":"Aberrant expression of NOS isoforms in Alzheimer\u2019s disease is structurally related to nitrotyrosine formation","volume":"953","author":"L\u00fcth","year":"2002","journal-title":"Brain Res."},{"key":"ref150","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/s41398-021-01349-z","article-title":"Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer\u2019s disease","volume":"11","author":"Lyra e Silva","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref151","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13041-017-0300-4","article-title":"Amyotrophic lateral sclerosis patient iPSC-derived astrocytes impair autophagy via non-cell autonomous mechanisms","volume":"10","author":"Madill","year":"2017","journal-title":"Mol. Brain"},{"key":"ref152","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1101\/gr.096826.109","article-title":"Widespread and tissue specific age-related DNA methylation changes in mice","volume":"20","author":"Maegawa","year":"2010","journal-title":"Genome Res."},{"key":"ref153","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1002\/cne.903580105","article-title":"Locus coeruleus cell loss in the aging human brain: A non-random process","volume":"358","author":"Manaye","year":"1995","journal-title":"J. Comp. Neurol."},{"key":"ref154","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1038\/s41591-021-01414-6","article-title":"Altered perivascular fibroblast activity precedes ALS disease onset","volume":"27","author":"M\u00e5nberg","year":"2021","journal-title":"Nat. Med."},{"key":"ref155","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3389\/fncel.2020.00016","article-title":"Cellular senescence in neurodegenerative diseases","volume":"14","author":"Mart\u00ednez-Cu\u00e9","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref156","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s00401-020-02248-1","article-title":"The mechanistic link between selective vulnerability of the locus coeruleus and neurodegeneration in Alzheimer\u2019s disease","volume":"141","author":"Matchett","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref157","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.3389\/fimmu.2020.01416","article-title":"Crosstalk Between astrocytes and microglia: An overview","volume":"11","author":"Matejuk","year":"2020","journal-title":"Front. Immunol."},{"key":"ref158","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41586-019-1195-2","article-title":"Single-cell transcriptomic analysis of Alzheimer\u2019s disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"ref159","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41586-021-03734-6","article-title":"Astrocytic interleukin-3 programs microglia and limits Alzheimer\u2019s disease","volume":"595","author":"McAlpine","year":"2021","journal-title":"Nature"},{"key":"ref160","doi-asserted-by":"publisher","first-page":"927","DOI":"10.3390\/brainsci11070927","article-title":"Aging-related tau astrogliopathy in aging and neurodegeneration","volume":"11","author":"McCann","year":"2021","journal-title":"Brain Sci."},{"key":"ref161","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1478-811X-11-34","article-title":"Complexity of dopamine metabolism","volume":"11","author":"Meiser","year":"2013","journal-title":"Cell Commun. Signal"},{"key":"ref162","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/S0306-4522(99)00455-8","article-title":"The absence of reactive astrocytosis is indicative of a unique inflammatory process in Parkinson\u2019s disease","volume":"95","author":"Mirza","year":"1999","journal-title":"Neuroscience"},{"key":"ref163","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.brainres.2004.09.014","article-title":"Direct evidence for expression of dopamine receptors in astrocytes from basal ganglia","volume":"1029","author":"Miyazaki","year":"2004","journal-title":"Brain Res."},{"key":"ref164","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1002\/jnr.22594","article-title":"Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis","volume":"89","author":"Miyazaki","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref165","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1002\/cne.24610","article-title":"Astrocytic changes with aging and Alzheimer\u2019s disease-type pathology in chimpanzees","volume":"527","author":"Munger","year":"2019","journal-title":"J. Comp. Neurol."},{"key":"ref166","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/jnr.24967","article-title":"Light microscopic and heterogeneity analysis of astrocytes in the common marmoset brain","volume":"99","author":"Mu\u00f1oz","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref167","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1111\/j.1476-5381.2009.00526.x","article-title":"Pharmacology of epigenetics in brain disorders","volume":"159","author":"Narayan","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref168","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1021\/bi401606f","article-title":"Rare individual amyloid-\u03b2 oligomers act on astrocytes to initiate neuronal damage","volume":"53","author":"Narayan","year":"2014","journal-title":"Biochemistry"},{"key":"ref169","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1093\/brain\/awz099","article-title":"Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report","volume":"142","author":"Nelson","year":"2019","journal-title":"Brain"},{"key":"ref170","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"ref171","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/0197-4580(93)90100-P","article-title":"GFAP mRNA increases with age in rat and human brain","volume":"14","author":"Nichols","year":"1993","journal-title":"Neurobiol. Aging"},{"key":"ref172","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.neulet.2010.03.041","article-title":"Valproic acid stimulates clusterin expression in human astrocytes: implications for Alzheimer\u2019s disease","volume":"475","author":"Nuutinen","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref173","doi-asserted-by":"publisher","first-page":"2496","DOI":"10.1007\/s11064-012-0818-x","article-title":"Norepinephrine: A neuromodulator that boosts the function of multiple cell types to optimize CNS performance","volume":"37","author":"O\u2019Donnell","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref174","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1523\/JNEUROSCI.4707-08.2009","article-title":"Uniquely hominid features of adult human astrocytes","volume":"29","author":"Oberheim","year":"2009","journal-title":"J. Neurosci."},{"key":"ref175","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.tins.2006.08.004","article-title":"Astrocytic complexity distinguishes the human brain","volume":"29","author":"Oberheim","year":"2006","journal-title":"Trends Neurosci."},{"key":"ref176","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/s41467-020-14378-x","article-title":"Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance","volume":"24","author":"Oe","year":"2020","journal-title":"Nat. Commun."},{"key":"ref177","doi-asserted-by":"publisher","first-page":"481","DOI":"10.3233\/JAD-180325","article-title":"Glial fibrillary acidic protein in serum is increased in Alzheimer\u2019s disease and correlates with cognitive impairment","volume":"67","author":"Oeckl","year":"2019","journal-title":"J. Alzheimers Dis."},{"key":"ref178","doi-asserted-by":"publisher","first-page":"e13296","DOI":"10.1111\/acel.13296","article-title":"Whole-body senescent cell clearance alleviates age-related brain inflammation and cognitive impairment in mice","volume":"20","author":"Ogrodnik","year":"2021","journal-title":"Aging Cell"},{"key":"ref179","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s12974-020-01774-9","article-title":"Transcriptomic profiling of microglia and astrocytes throughout aging","volume":"17","author":"Pan","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref180","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s40478-021-01180-z","article-title":"Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer\u2019s disease","volume":"9","author":"Park","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref181","doi-asserted-by":"publisher","first-page":"639428","DOI":"10.3389\/fnagi.2021.639428","article-title":"A meta-analysis of brain DNA methylation across sex, age, and alzheimer\u2019s disease points for accelerated epigenetic aging in neurodegeneration","volume":"13","author":"Pellegrini","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref182","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1093\/brain\/awab223","article-title":"Plasma GFAP is an early marker of amyloid-\u03b2 but not tau pathology in Alzheimer\u2019s disease","volume":"144","author":"Pereira","year":"2021","journal-title":"Brain"},{"key":"ref183","doi-asserted-by":"publisher","first-page":"168","DOI":"10.3390\/brainsci10030168","article-title":"No longer underappreciated: the emerging concept of astrocyte heterogeneity in neuroscience","volume":"10","author":"Pestana","year":"2020","journal-title":"Brain Sci."},{"key":"ref184","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1172\/JCI71601","article-title":"Emerging mechanisms of molecular pathology in ALS","volume":"125","author":"Peters","year":"2015","journal-title":"J. Clin. Invest."},{"key":"ref185","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.neurobiolaging.2016.05.003","article-title":"Neurofilament-labeled pyramidal neurons and astrocytes are deficient in DNA methylation marks in Alzheimer\u2019s disease","volume":"45","author":"Phipps","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref186","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1002\/pmic.200300456","article-title":"Analysis of gial acidic fibrillary protein in the human entorhinal cortex during aging and in Alzheimer\u2019s disease","volume":"3","author":"Porchet","year":"2003","journal-title":"Proteomics"},{"key":"ref187","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.mcn.2015.02.015","article-title":"The degree of astrocyte activation in multiple system atrophy is inversely proportional to the distance to \u03b1-synuclein inclusions","volume":"65","author":"Radford","year":"2015","journal-title":"Mol. Cell. Neurosci."},{"key":"ref188","doi-asserted-by":"publisher","first-page":"e9665","DOI":"10.15252\/emmm.201809665","article-title":"Inhibition of Stat3-mediated astrogliosis ameliorates pathology in an Alzheimer\u2019s disease model","volume":"11","author":"Reichenbach","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref189","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1038\/s41593-020-00728-x","article-title":"Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer\u2019s disease","volume":"23","author":"Richetin","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref190","doi-asserted-by":"publisher","first-page":"fcaa109","DOI":"10.1093\/braincomms\/fcaa109","article-title":"Anti-inflammatories in Alzheimer\u2019s disease\u2014potential therapy or spurious correlate?","volume":"2","author":"Rivers-Auty","year":"2020","journal-title":"Brain Commun."},{"key":"ref191","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1093\/brain\/awy146","article-title":"Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated","volume":"141","author":"Robinson","year":"2018","journal-title":"Brain"},{"key":"ref192","doi-asserted-by":"publisher","first-page":"9372182","DOI":"10.1155\/2019\/9372182","article-title":"Activators and inhibitors of NRF2: a review of their potential for clinical development","volume":"2019","author":"Robledinos-Ant\u00f3n","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref193","doi-asserted-by":"publisher","first-page":"536682","DOI":"10.3389\/fnins.2020.536682","article-title":"Mitochondrial metabolism in astrocytes regulates brain bioenergetics, neurotransmission and redox balance","volume":"14","author":"Rose","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref194","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s12974-020-01776-7","article-title":"Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson\u2019s disease brain","volume":"17","author":"Rostami","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref195","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s00281-015-0515-3","article-title":"Control of autoimmune CNS inflammation by astrocytes","volume":"37","author":"Rothhammer","year":"2015","journal-title":"Semin. Immunopathol."},{"key":"ref196","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/ana.410380114","article-title":"Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis","volume":"38","author":"Rothstein","year":"1995","journal-title":"Ann. Neurol."},{"key":"ref197","doi-asserted-by":"publisher","first-page":"e51696","DOI":"10.15252\/embr.202051696","article-title":"SFRP1 modulates astrocyte-to-microglia crosstalk in acute and chronic neuroinflammation","volume":"22","author":"Rueda-Carrasco","year":"2021","journal-title":"EMBO Rep."},{"key":"ref198","doi-asserted-by":"publisher","first-page":"108895","DOI":"10.1016\/j.celrep.2021.108895","article-title":"TNF-\u03b1 and \u03b1-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration","volume":"34","author":"Russ","year":"2021","journal-title":"Cell Rep."},{"key":"ref199","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1038\/nm.4397","article-title":"Microglia emerge as central players in brain disease","volume":"23","author":"Salter","year":"2017","journal-title":"Nat. Med."},{"key":"ref200","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.mcn.2017.10.001","article-title":"CHI3L1 and CHI3L2 overexpression in motor cortex and spinal cord of sALS patients","volume":"85","author":"Sanfilippo","year":"2017","journal-title":"Mol. Cell. Neurosci."},{"key":"ref201","doi-asserted-by":"publisher","first-page":"e1800105","DOI":"10.1002\/prca.201800105","article-title":"Quantitative proteomic profiling of cerebrospinal fluid to identify candidate biomarkers for alzheimer\u2019s disease","volume":"13","author":"Sathe","year":"2019","journal-title":"Proteomics Clin. Appl."},{"key":"ref202","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/0022-510X(96)00073-1","article-title":"Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis","volume":"139","author":"Schiffer","year":"1996","journal-title":"J. Neurol. Sci."},{"key":"ref203","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41586-019-1404-z","article-title":"Neuronal vulnerability and multilineage diversity in multiple sclerosis","volume":"573","author":"Schirmer","year":"2019","journal-title":"Nature"},{"key":"ref204","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1016\/j.ajpath.2013.02.031","article-title":"A phenotypic change but not proliferation underlies glial responses in Alzheimer disease","volume":"182","author":"Serrano-Pozo","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref205","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1006\/bbrc.1997.7460","article-title":"Functional elements in molecular chaperone \u03b1-crystallin: identification of binding sites in \u03b1B-crystallin","volume":"239","author":"Sharma","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref206","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.1523\/JNEUROSCI.23-08-03394.2003","article-title":"Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress","volume":"23","author":"Shih","year":"2003","journal-title":"J. Neurosci."},{"key":"ref207","doi-asserted-by":"publisher","first-page":"537","DOI":"10.3389\/fphar.2020.00537","article-title":"Histone deacetylases inhibitors in neurodegenerative diseases, neuroprotection and neuronal differentiation","volume":"11","author":"Shukla","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref208","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s40478-017-0478-9","article-title":"Astrocytes in mouse models of tauopathies acquire early deficits and lose neurosupportive functions","volume":"5","author":"Sidoryk-Wegrzynowicz","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref209","doi-asserted-by":"publisher","first-page":"12552","DOI":"10.1038\/s41598-018-30675-4","article-title":"Astrocyte-specific overexpression of Nrf2 protects against optic tract damage and behavioural alterations in a mouse model of cerebral hypoperfusion","volume":"8","author":"Sigfridsson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref210","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13041-020-00569-6","article-title":"Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity","volume":"13","author":"Singh","year":"2020","journal-title":"Mol. Brain"},{"key":"ref211","doi-asserted-by":"publisher","first-page":"101059","DOI":"10.1016\/j.redox.2018.11.017","article-title":"NRF2 and NF-\u049bB interplay in cerebrovascular and neurodegenerative disorders: molecular mechanisms and possible therapeutic approaches","volume":"21","author":"Sivandzade","year":"2019","journal-title":"Redox Biol."},{"key":"ref212","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1093\/brain\/awz419","article-title":"Distinct responses of neurons and astrocytes to TDP-43 proteinopathy in amyotrophic lateral sclerosis","volume":"143","author":"Smethurst","year":"2020","journal-title":"Brain"},{"key":"ref213","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.neuron.2019.12.014","article-title":"Astrocyte unfolded protein response induces a specific reactivity state that causes non-cell-autonomous neuronal degeneration","volume":"105","author":"Smith","year":"2020","journal-title":"Neuron"},{"key":"ref214","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.1523\/JNEUROSCI.17-08-02653.1997","article-title":"Widespread peroxynitrite-mediated damage in Alzheimer\u2019s disease","volume":"17","author":"Smith","year":"1997","journal-title":"J. Neurosci."},{"key":"ref215","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nrn3898","article-title":"Astrocyte barriers to neurotoxic inflammation","volume":"16","author":"Sofroniew","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref216","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: biology and pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref217","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.celrep.2016.12.011","article-title":"Major shifts in glial regional identity are a transcriptional hallmark of human brain aging","volume":"18","author":"Soreq","year":"2017","journal-title":"Cell Rep."},{"key":"ref218","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/nature25975","article-title":"Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults","volume":"555","author":"Sorrells","year":"2018","journal-title":"Nature"},{"key":"ref219","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-019-01977-2","article-title":"\u03b1-Synuclein and astrocytes: tracing the pathways from homeostasis to neurodegeneration in Lewy body disease","volume":"138","author":"Sorrentino","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref220","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.3390\/cells9112415","article-title":"An overview of astrocyte responses in genetically induced alzheimer\u2019s disease mouse models","volume":"9","author":"Spanos","year":"2020","journal-title":"Cell"},{"key":"ref221","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.neurobiolaging.2018.10.007","article-title":"Phenotypic and functional differences between senescent and aged murine microglia","volume":"74","author":"Stojiljkovic","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref222","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.tma.2019.01.002","article-title":"Senescence in aging and disorders of the central nervous system","volume":"3","author":"Swenson","year":"2019","journal-title":"Transl. Med. Aging"},{"key":"ref223","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1017\/S1461145714000698","article-title":"Shortened telomere length in white matter oligodendrocytes in major depression: potential role of oxidative stress","volume":"17","author":"Szebeni","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref224","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/S0531-5565(96)00036-8","article-title":"Senescence-accelerated mouse (SAM): a novel murine model of senescence","volume":"32","author":"Takeda","year":"1997","journal-title":"Exp. Gerontol."},{"key":"ref225","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.nbd.2015.06.010","article-title":"Low levels of astroglial markers in Parkinson\u2019s disease: relationship to \u03b1-synuclein accumulation","volume":"82","author":"Tong","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref226","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1038\/emboj.2013.122","article-title":"Expression of ALS-linked TDP-43 mutant in astrocytes causes non-cell-autonomous motor neuron death in rats","volume":"32","author":"Tong","year":"2013","journal-title":"EMBO J."},{"key":"ref227","doi-asserted-by":"publisher","first-page":"420957","DOI":"10.1155\/2012\/420957","article-title":"Dementia in Parkinson\u2019s disease correlates with \u03b1-synuclein pathology but not with cortical astrogliosis","volume":"2012","author":"Van Den Berge","year":"2012","journal-title":"Parkinson. Dis."},{"key":"ref228","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/nsb722","article-title":"Crystal structure and assembly of a eukaryotic small heat shock protein","volume":"8","author":"Van Montfort","year":"2001","journal-title":"Nat. Struct. Biol."},{"key":"ref229","doi-asserted-by":"publisher","first-page":"6003","DOI":"10.1038\/s41598-020-62864-5","article-title":"Astrocytes with TDP-43 inclusions exhibit reduced noradrenergic cAMP and Ca2+ signaling and dysregulated cell metabolism","volume":"10","author":"Velebit","year":"2020","journal-title":"Sci. Rep."},{"key":"ref230","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s13195-020-00682-7","article-title":"Combination of plasma amyloid beta(1-42\/1-40)and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology","volume":"12","author":"Verberk","year":"2020","journal-title":"Alzheimers Res. Ther."},{"key":"ref231","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1152\/physrev.00042.2016","article-title":"Physiology of astroglia","volume":"98","author":"Verkhratsky","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref232","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/B978-0-12-811060-7.00021-8","article-title":"Epigenetic drugs for cancer and precision medicine","author":"Verma","year":"2018","journal-title":"Epigenetics of Aging and Longevity."},{"key":"ref233","doi-asserted-by":"publisher","first-page":"e12753","DOI":"10.1111\/nan.12753","article-title":"Systematic review of human post-mortem immunohistochemical studies and bioinformatics analyses unveil the complexity of astrocyte reaction in Alzheimer\u2019s disease","volume":"48","author":"Viejo","year":"2021","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref234","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1084\/jem.184.4.1425","article-title":"Inducible nitric oxide synthase in tangle-bearing neurons of patients with Alzheimer\u2019s disease","volume":"184","author":"Vodovotz","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref235","doi-asserted-by":"publisher","first-page":"5615","DOI":"10.1093\/nar\/gkw159","article-title":"Repurposing the CRISPR-Cas9 system for targeted DNA methylation","volume":"44","author":"Vojta","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref236","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1007\/s11825-018-0185-3","article-title":"Current knowledge and recent insights into the genetic basis of amyotrophic lateral sclerosis","volume":"30","author":"Volk","year":"2018","journal-title":"Med. Genet."},{"key":"ref237","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1176\/ajp.155.3.344","article-title":"Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals","volume":"155","author":"Volkow","year":"1998","journal-title":"Am. J. Psychiatry"},{"key":"ref238","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nrn3725","article-title":"Astrocyte Ca2+ signalling: An unexpected complexity","volume":"15","author":"Volterra","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref239","doi-asserted-by":"publisher","first-page":"12844","DOI":"10.18632\/aging.102557","article-title":"Targeting senescent cells: approaches, opportunities, challenges","volume":"11","author":"von Kobbe","year":"2019","journal-title":"Aging"},{"key":"ref240","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1136\/jnnp-2019-321916","article-title":"Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes","volume":"91","author":"Vu","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref241","doi-asserted-by":"publisher","first-page":"645691","DOI":"10.3389\/fncel.2021.645691","article-title":"Astrocytes, noradrenaline, \u03b11-adrenoreceptors, and neuromodulation: evidence and unanswered questions","volume":"15","author":"Wahis","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref242","doi-asserted-by":"publisher","first-page":"31","DOI":"10.17879\/freeneuropathology-2020-3025","article-title":"A\u03b2 Plaques","volume":"1","author":"Walker","year":"2020","journal-title":"Free Neuropathol."},{"key":"ref601","doi-asserted-by":"publisher","first-page":"5748","DOI":"10.1038\/s41598-021-85061-4","article-title":"Gene co-expression network analysis in human spinal cord highlights mechanisms underlying amyotrophic lateral sclerosis susceptibility","volume":"11","author":"Wang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref243","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41467-020-20322-w","article-title":"Filamentous recombinant human tau activates primary astrocytes via an integrin receptor complex","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref244","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s40478-021-01244-0","article-title":"Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS","volume":"9","author":"Waters","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref245","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.tins.2018.01.010","article-title":"Long road to ruin: noradrenergic dysfunction in neurodegenerative disease","volume":"41","author":"Weinshenker","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref246","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41586-020-1999-0","article-title":"MAFG-driven astrocytes promote CNS inflammation","volume":"578","author":"Wheeler","year":"2020","journal-title":"Nature"},{"key":"ref247","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1016\/j.celrep.2019.07.060","article-title":"Complement C3 is activated in human AD brain and is required for neurodegeneration in mouse models of amyloidosis and tauopathy","volume":"28","author":"Wu","year":"2019","journal-title":"Cell Rep."},{"key":"ref248","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/s41386-018-0151-4","article-title":"Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling","volume":"44","author":"Xin","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref249","doi-asserted-by":"publisher","first-page":"e13465","DOI":"10.1111\/acel.13465","article-title":"YAP prevents premature senescence of astrocytes and cognitive decline of Alzheimer\u2019s disease through regulating CDK6 signaling","volume":"20","author":"Xu","year":"2021","journal-title":"Aging Cell"},{"key":"ref250","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1089\/hum.2015.067","article-title":"CRISPR\/Cas9-mediated genome editing of epigenetic factors for cancer therapy","volume":"26","author":"Yao","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref251","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1159\/000330254","article-title":"Repeated lipopolysaccharide stimulation induces cellular senescence in BV2 cells","volume":"19","author":"Yu","year":"2012","journal-title":"Neuroimmunomodulation"},{"key":"ref252","doi-asserted-by":"publisher","first-page":"6391","DOI":"10.1523\/JNEUROSCI.6221-11.2012","article-title":"Genomic analysis of reactive astrogliosis","volume":"32","author":"Zamanian","year":"2012","journal-title":"J. Neurosci."},{"key":"ref253","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/BF03325217","article-title":"A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer\u2019s disease","volume":"21","author":"Zanetti","year":"2009","journal-title":"Aging Clin. Exp. Res."},{"key":"ref254","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/s41593-019-0372-9","article-title":"Senolytic therapy alleviates A\u03b2-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer\u2019s disease model","volume":"22","author":"Zhang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref255","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1002\/glia.23761","article-title":"Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology","volume":"68","author":"Zhao","year":"2020","journal-title":"Glia"},{"key":"ref256","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41591-019-0695-9","article-title":"Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer\u2019s disease","volume":"26","author":"Zhou","year":"","journal-title":"Nat. Med."},{"key":"ref257","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1080\/13543776.2020.1715365","article-title":"Recent progress in the development of small molecule Nrf2 activators: a patent review (2017-present)","volume":"30","author":"Zhou","year":"","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref258","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/acel.12445","article-title":"Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors","volume":"15","author":"Zhu","year":"2016","journal-title":"Aging Cell"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.814889\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T12:50:28Z","timestamp":1647521428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.814889\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":259,"alternative-id":["10.3389\/fphys.2022.814889"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.814889","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]},"article-number":"814889"}}