Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration
Open accessAbstract
Despite advances in uncovering the mechanisms that underlie neuroinflammation and neurodegenerative disease, therapies that prevent neuronal loss remain elusive. Targeting of disease-defining markers in conditions such as Alzheimer disease (amyloid-β and tau) or Parkinson disease (α-synuclein) has been met with limited success, suggesting that these proteins do not act in isolation but form part of a pathological network. This network could involve phenotypic alteration of multiple cell types in the CNS, including astrocytes, which have a major neurosupportive, homeostatic role in the healthy CNS but adopt reactive states under acute or chronic adverse conditions. Transcriptomic studies in human patients and disease models have revealed the co-existence of many putative reactive sub-states of astrocytes. Inter-disease and even intra-disease heterogeneity of reactive astrocytic sub-states are well established, but the extent to which specific sub-states are shared across different diseases is unclear. In this Review, we highlight how single-cell and single-nuclei RNA sequencing and other 'omics' technologies can enable the functional characterization of defined reactive astrocyte states in various pathological scenarios. We provide an integrated perspective, advocating cross-modal validation of key findings to define functionally important sub-states of astrocytes and their triggers as tractable therapeutic targets with cross-disease relevance.
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Astrocyte and microglia iPSC models partially recapitulate the transcriptomes of their in vivo counterparts and may capture authentic neurodegenerative disease phenotypes.
“Astrocyte and microglia iPSC models partially recapitulate the transcriptomes of their in vivo counterparts and may capture authentic neurodegenerative disease phenotypes [345,406,480,481,482,483,484].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [406]
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Self-citation
- Authors
- Patani, R., Hardingham, G. E., & Liddelow, S. A.
- Affiliations
- The Francis Crick Institute (GB)
- UK Dementia Research Institute (GB)
- NYU Langone Health (US)
- Corresponding author
- Liddelow, Shane A.
- Venue
- Nature Reviews Neurology
- Published
- 2023-06-12
- Volume
- 19
- Issue
- 7
- Pages
- 395-409
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W4380367860
- Cited by
- 531
- References
- 46
- Citations by year
- 2026: 140 · 2025: 202 · 2024: 162 · 2023: 26 · 2021: 1
- FWCI
- 14.01
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Licence
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council (MR/S006591/1)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- reactive astrocytes, astrocyte heterogeneity, neuroinflammation, neurodegeneration, Alzheimer's disease, Parkinson's disease, amyloid-beta, tau protein, alpha-synuclein, single-cell RNA sequencing, single-nucleus RNA sequencing, therapeutic target
- MeSH terms
- Neuroinflammatory Diseases, Alzheimer Disease, Astrocytes, Humans, Parkinson Disease, Neurodegenerative Diseases
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