Astrocytes in selective vulnerability to neurodegenerative disease.

TitleAstrocytes in selective vulnerability to neurodegenerative disease.
Publication TypeJournal Article
Year of Publication2024
AuthorsZimmer TS, Orr AL, Orr AG
JournalTrends Neurosci
Volume47
Issue4
Pagination289-302
Date Published2024 Apr
ISSN1878-108X
KeywordsAstrocytes, Brain, Humans, Neurodegenerative Diseases, Neurons
Abstract

Selective vulnerability of specific brain regions and cell populations is a hallmark of neurodegenerative disorders. Mechanisms of selective vulnerability involve neuronal heterogeneity, functional specializations, and differential sensitivities to stressors and pathogenic factors. In this review we discuss the growing body of literature suggesting that, like neurons, astrocytes are heterogeneous and specialized, respond to and integrate diverse inputs, and induce selective effects on brain function. In disease, astrocytes undergo specific, context-dependent changes that promote different pathogenic trajectories and functional outcomes. We propose that astrocytes contribute to selective vulnerability through maladaptive transitions to context-divergent phenotypes that impair specific brain regions and functions. Further studies on the multifaceted roles of astrocytes in disease may provide new therapeutic approaches to enhance resilience against neurodegenerative disorders.

DOI10.1016/j.tins.2024.02.008
Alternate JournalTrends Neurosci
PubMed ID38521710
PubMed Central IDPMC11006581
Grant ListR01 AG068091 / AG / NIA NIH HHS / United States
RF1 NS118569 / NS / NINDS NIH HHS / United States