Cited by 662Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchAlzheimer's disease research and treatments

Function and therapeutic value of astrocytes in neurological diseases

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Lee, Hong-Gyun, Wheeler, Michael A., Quintana, Francisco J.·2022·Nature Reviews Drug Discovery

Abstract

Astrocytes are abundant glial cells in the central nervous system (CNS) that perform diverse functions in health and disease. Astrocyte dysfunction is found in numerous diseases, including multiple sclerosis, Alzheimer disease, Parkinson disease, Huntington disease and neuropsychiatric disorders. Astrocytes regulate glutamate and ion homeostasis, cholesterol and sphingolipid metabolism and respond to environmental factors, all of which have been implicated in neurological diseases. Astrocytes also exhibit significant heterogeneity, driven by developmental programmes and stimulus-specific cellular responses controlled by CNS location, cell-cell interactions and other mechanisms. In this Review, we highlight general mechanisms of astrocyte regulation and their potential as therapeutic targets, including drugs that alter astrocyte metabolism, and therapies that target transporters and receptors on astrocytes. Emerging ideas, such as engineered probiotics and glia-to-neuron conversion therapies, are also discussed. We further propose a concise nomenclature for astrocyte subsets that we use to highlight the roles of astrocytes and specific subsets in neurological diseases.

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  • Astrocytes are implicated in various brain pathologies, including neurodevelopmental conditions such as FXS.

    “Astrocytes are implicated in various brain pathologies (Lee et al., 2022), including neurodevelopmental conditions such as fragile X syndrome (FXS, Fernández-Blanco and Dierssen, 2020).”

    From Astrocytes in fragile X syndrome (2024) · cites this paper as Lee et al., 2022

  • Astrocytic calcium signaling underlies vital physiological functions, and its dysregulation is associated with neuroinflammation and neurodegeneration.

    “The astrocytic calcium signaling underlies vital physiological functions, and its dysregulation has been associated with neuroinflammation and neurodegeneration.246,252”

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Authors
Lee, H.-G., Wheeler, M. A., & Quintana, F. J.
Affiliations
  • Brigham and Women's Hospital (US)
  • Broad Institute (US)
Corresponding author
Quintana, Francisco J.
Venue
Nature Reviews Drug Discovery
Published
2022-02-16
Volume
21
Issue
5
Pages
339-358
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
OpenAlex
W4213362614
Cited by
662
References
320
Citations by year
2026: 132 · 2025: 220 · 2024: 176 · 2023: 99 · 2022: 34
FWCI
13.63
Type
journal article
Language
en
Open access
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Repositorio Institucional (Pontificia Universidad Javeriana) (submittedVersion, other-oa)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
Funders
  • Ministerio de Ciencia, Tecnología e Innovación
  • Pontificia Universidad Javeriana
  • National Institute of Allergy and Infectious Diseases (R01AI149699, R01AI126880)
  • National Institute of Neurological Disorders and Stroke (F32NS101790, R01NS102807, K99NS114111, R00NS114111)
  • National Institute of Environmental Health Sciences (R01ES029136)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
astrocytes, astrocyte dysfunction, neurological disorders, astrocyte heterogeneity, glutamate homeostasis, ion homeostasis, cholesterol metabolism, sphingolipid metabolism, astrocyte metabolism, engineered probiotics, glia-to-neuron conversion, multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, neuropsychiatric disorders, therapeutic target
MeSH terms
Astrocytes, Cell Communication, Humans, Multiple Sclerosis, Nervous System Diseases, Glutamic Acid

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