The DOI matches its Crossref record; 320 of the 320 references it cites were found in a registry or an index.
Function and therapeutic value of astrocytes in neurological diseases
Open accessAbstract
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 (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
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“The astrocytic calcium signaling underlies vital physiological functions, and its dysregulation has been associated with neuroinflammation and neurodegeneration.246,252”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [246]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Molecular basis of astrocyte diversity and morphology across the CNS in health and disease
Endo, F., Kasai, A., Soto, J. S., Yu, X., Qu, Z., Hashimoto, H., Gradinaru, V., Kawaguchi, R., & Khakh, B. S. (2022) · Science · doi:10.1126/science.adc9020 · Cited by 560
Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders
Brandebura, A. N., Paumier, A., Onur, T. S., & Allen, N. J. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-022-00641-1 · Cited by 427
Astrocytes in the initiation and progression of epilepsy
Vezzani, A., Ravizza, T., Bedner, P., Aronica, E., Steinhäuser, C., & Boison, D. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00727-5 · Cited by 272
Lei, W., Cheng, Y., Liu, X., Gao, J., Zhu, Z., Ding, W., Xu, X., Li, Y., Ling, Z., Jiang, R., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1582119 · Cited by 68
Metadata
- 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
- 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
- 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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