Reactive Astrocytes: Production, Function, and Therapeutic Potential
Open accessAbstract
Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma. In this review, we summarize recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful. We will also discuss new methods for purifying and investigating reactive-astrocyte functions and provide an overview of new markers for delineating these different states of reactive astrocytes. The discovery that astrocytes have different types of reactive states has important implications for the development of new therapies for CNS injury and diseases.
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Reactive astrocytes probably secrete additional factors that affect microglia-mediated neuroinflammatory behaviors.
“In turn, reactive astrocytes probably secrete additional factors that affect microglia-mediated neuroinflammatory behaviors [408].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [408]
Many studies show an increase in NF-κB in the AD brain.
“Many studies show an increase in NF-κB in the AD brain (Liddelow and Barres, 2017).”
From APOE2, E3, and E4 differentially modulate cellular homeostasis, cholesterol metabolism, and inflammatory response in isogenic iPSC-derived astrocytes (2022) · cites this paper as Liddelow and Barres, 2017
Reactive astrocytes exhibit hypertrophic characteristics with thick and long processes and increased expression level of glial fibrillary acidic protein (GFAP).
“The reactive astrocytes exhibit hypertrophic characteristics with thick and long processes and increased expression level of glial fibrillary acidic protein (GFAP; Liddelow and Barres, 2017;Escartin et al., 2021).”
From Cell Adhesion Molecule Protocadherin-γC5 Ameliorates Aβ Plaque Pathogenesis by Modulating Astrocyte Function in Alzheimer's Disease (2025) · cites this paper as Liddelow and Barres, 2017
Astrocytes are immune-competent; they respond to a wide range of brain insults and are activated in a wide range of neurodegenerative diseases including Alzheimer's disease.
“However, astrocytes are immune-competent. They respond to a wide range of brain insults and are activated in a wide range of neurodegenerative diseases including Alzheimer’s disease9,69–71.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [71]
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References 109 · Cited by 2,336
- Authors
- Liddelow, S. A., & Barres, B. A.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Liddelow, Shane A.
- Barres, Ben A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 46
- Issue
- 6
- Pages
- 957-967
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2700330585
- Semantic Scholar
- e312ecd8d31f75530d005a763f46ca3876069602
- Cited by
- 2,336
- References
- 109
- Citations by year
- 2026: 213 · 2025: 255 · 2024: 335 · 2023: 292 · 2022: 301 · 2021: 357 · 2020: 264 · 2019: 193 · 2018: 104 · 2017: 20
- FWCI
- 15.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- reactive astrocytes, astrocyte heterogeneity, central nervous system injury, neurodegenerative diseases, neuroinflammation, astrocyte markers
- MeSH terms
- Animals, Astrocytes, Biological Therapy, Brain, Central Nervous System, Humans, Neurons, Neurodegenerative Diseases
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