ArticleThe Journal of clinical investigation2022
SIRT1 inactivation switches reactive astrocytes to an antiinflammatory phenotype in CNS autoimmunity.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- CRISPR and Myelin regeneration: a systematic review of applications in demyelinating CNS Disorders, with a focus on MS.Regenerative medicine · 2025Pooled it
- Review
- Astrocyte Functional Heterogeneity in Multiple Sclerosis.Journal of clinical neurology (Seoul, Korea) · 2026Review
- Astrocytes in neuroinflammation and brain cancer.Molecular biomedicine · 2026Review
- Microglial HDAC3 inhibits the migration of CD8-positive T cell in the development of EAE by restraining the expression of CCL5.Cell & bioscience · 2026Article
- Engineered Small Extracellular Vesicles Targeting Tumor-Associated Endothelial Cells to Effectively Remodel the Glioma Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The effect of astrocyte depletion and repopulation approaches in pathological condition of CNS.Acta neurologica Belgica · 2026Review
- Glial cell crosstalk in Parkinson's disease: Mechanisms, implications, and therapeutic strategies.Fundamental research · 2025Review
- Increased reactive astrocytes in hippocampal CA1 region mediated by decreased CXCR7 is involved in postoperative cognitive dysfunction in aged mice.Cell biology and toxicology · 2025Article
- Osteoblast-CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Reactive Astrocytes in Glioma: Emerging Opportunities and Challenges.International journal of molecular sciences · 2025Review
- Activation and inhibition of sirtuins: From bench to bedside.Medicinal research reviews · 2025Review
- Sirt1 protects lupus nephritis by inhibiting the NLRP3 signaling pathway in human glomerular mesangial cells.Open life sciences · 2025Article
- Bone-protective effects of neutralizing angiopoietin-like protein 4 monoclonal antibody in rheumatoid arthritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Redox-sensitive epigenetic activation of SUV39H1 contributes to liver ischemia-reperfusion injury.Redox biology · 2024Article
- Mechanisms of Transsynaptic Degeneration in the Aging Brain.Aging and disease · 2024Review
- Beneficial Effects ofNutrients · 2024Review
- Inhibiting the NLRP3 Inflammasome with MCC950 Alleviates Neurological Impairment in the Brain of EAE Mice.Molecular neurobiology · 2024Article
- Lack of the Histone Deacetylase SIRT1 Leads to Protection against Endoplasmic Reticulum Stress through the Upregulation of Heat Shock Proteins.International journal of molecular sciences · 2024Article
- Isthmin-1 Improves Aging-Related Cardiac Dysfunction in Mice through Enhancing Glycolysis and SIRT1 Deacetylase Activity.Aging and disease · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Astrocytes are highly heterogeneous in their phenotype and function, which contributes to CNS disease, repair, and aging; however, the molecular mechanism of their functional states remains largely unknown. Here, we show that activation of sirtuin 1 (SIRT1), a protein deacetylase, played an important role in the detrimental actions of reactive astrocytes, whereas its inactivation conferred these cells with antiinflammatory functions that inhibited the production of proinflammatory mediators by myeloid cells and microglia and promoted the differentiation of oligodendrocyte progenitor cells. Mice with astrocyte-specific Sirt1 knockout (Sirt1-/-) had suppressed progression of experimental autoimmune encephalomyelitis (EAE), an animal model of CNS inflammatory demyelinating disease. Ongoing EAE was also suppressed when Sirt1 expression in astrocytes was diminished by a CRISPR/Cas vector, resulting in reduced demyelination, decreased numbers of T cells, and an increased rate of IL-10-producing macrophages and microglia in the CNS, whereas the peripheral immune response remained unaffected. Mechanistically, Sirt1-/- astrocytes expressed a range of nuclear factor erythroid-derived 2-like 2 (Nfe2l2) target genes, and Nfe2l2 deficiency shifted the beneficial action of Sirt1-/- astrocytes to a detrimental one. These findings identify an approach for switching the functional state of reactive astrocytes that will facilitate the development of astrocyte-targeting therapies for inflammatory neurodegenerative diseases such as multiple sclerosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.