4.8 Review

Function and therapeutic value of astrocytes in neurological diseases

Journal

NATURE REVIEWS DRUG DISCOVERY
Volume 21, Issue 5, Pages 339-358

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41573-022-00390-x

Keywords

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Funding

  1. NIH [NS102807, ES02530, ES029136, AI126880, AI149699, 1K99NS114111, F32NS101790]
  2. National Multiple Sclerosis Society [RG4111A1]
  3. International Progressive MS Alliance [PA-1604-08459]
  4. National Research Foundation of Korea (NRF) - Ministry of Education [2021R1A6A3A14039088]
  5. Dana-Farber Cancer Institute [T32CA207201]
  6. Program in Interdisciplinary Neuroscience at Brigham and Women's Hospital
  7. Women's Brain Initiative at Brigham and Women's Hospital
  8. NIH
  9. National Research Foundation of Korea [2021R1A6A3A14039088] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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This review discusses astrocytes, a type of glial cell that is involved in various neurological diseases. Astrocytes regulate important processes in the central nervous system, such as glutamate and ion homeostasis, cholesterol and sphingolipid metabolism, and response to environmental factors. The review highlights the potential of targeting astrocytes for therapeutic intervention, including manipulating their metabolism and targeting transporters and receptors on astrocytes. The review also proposes a new nomenclature for astrocyte subsets to better understand their roles in neurological diseases.
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. In this Review, Quintana and colleagues discuss astrocytes, a type of glial cell that could be manipulated to treat neurological conditions. Potential astrocyte targets, and the progess made towards developing astrocyte-directed therapies, are highlighted, along with their potential pitfalls. They also propose a novel nomenclature for astrocyte subsets.

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