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

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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

DOI 10.1038/s41573-022-00390-xPMC PMC9081171

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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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See all 662

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.
ORCID: Lee, Hong-Gyun
Wheeler, Michael A.
Quintana, Francisco J.
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2022-02-16
Volume: 21
Issue: 5
Pages: 339-358
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/s41573-022-00390-x
PMC: PMC9081171
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: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Function and therapeutic value of astrocytes in neurological diseases

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