ArticleNature medicine2011
Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers, 2 of them syntheses that pooled it.
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Who cites it
210 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Neuronutraceuticals Combating Neuroinflammaging: Molecular Insights and Translational Challenges-A Systematic Review.Nutrients · 2022Pooled it
- Sirtuin Acetylation and Deacetylation: a Complex Paradigm in Neurodegenerative Disease.Molecular neurobiology · 2021Pooled it
- Irisin-BDNF axis mediates muscle-brain communication: a complete molecular cascade and potential bidirectional feedback from peripheral activation to central protection.Biogerontology · 2026Review
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Mitochondrial DNA homeostasis: A novel therapeutic target for neurodegenerative diseases.Neural regeneration research · 2026Article
- Asparagus Saponin Officinalisnin-II Alleviates Fluoride-Induced Neurotoxicity Via Activation of the SIRT1/BDNF Signaling Pathway.Biological trace element research · 2026Article
- Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease.EMBO molecular medicine · 2026Article
- A Potential Functional Food-Based Neuroprotective Strategy Using Mulberry Leaf Extract and Trolox Against HFoods (Basel, Switzerland) · 2026Article
- Epigenetic and Neurogenomic Mechanisms Linking Physical Activity to Brain Plasticity and Cognitive Function.Genes · 2026Review
- Topiramate protects against neuroinflammation in response to traumatic brain injury via activating Sirt1 signaling.Scientific reports · 2026Article
- Neuroprotection by canagliflozin in a Huntington's disease model: role of HIF-1α and PI3K/AKT signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Overview of Huntington's Disease and Emerging Treatment Strategies: A Narrative Review.Cureus · 2025Review
- Formulation and Evaluation of Astaxanthin-Loaded Invasomes as Therapeutic Approaches for Alzheimer's Disease Induced in Rats: Role of SIRT-1/BDNF/miRNA-134/GSK-3β Signaling.Molecular neurobiology · 2025Article
- Therapeutic applications of exercise in neurodegenerative diseases: focusing on the mechanism of SIRT1.Molecular and cellular biochemistry · 2025Review
- AI-Enhanced Transcriptomic Discovery of Druggable Targets and Repurposed Therapies for Huntington's Disease.Brain sciences · 2025Review
- Erythropoietin (EPO) Alleviates Chronic Stress-Induced Depression by Modulating SIRT1-Mediated Mitochondrial Function.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Multi-Target Protective Effects of β-Caryophyllene (BCP) at the Intersection of Neuroinflammation and Neurodegeneration.International journal of molecular sciences · 2025Article
- Niacin Modulates SIRT1-Driven Signaling to Counteract Radiation-Induced Neurocognitive and Behavioral Impairments.International journal of molecular sciences · 2025Article
- Antioxidant and Anti-Inflammatory Defenses in Huntington's Disease: Roles of NRF2 and PGC-1α, and Therapeutic Strategies.Life (Basel, Switzerland) · 2025Review
- Combining Network Pharmacology and Experimental Verification to Ascertain the Mechanism of Action of Asparagus officinalis Against the Brain Damage Caused by Fluorosis.Environmental toxicology · 2025Article
150 more citing papers are in PubMed but not listed here.
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10 authors at 4 institutions in 1 country.
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Abstract
Sirt1, a NAD-dependent protein deacetylase, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. Here we show that Sirt1 has a neuroprotective role in models of Huntington's disease, an inherited neurodegenerative disorder caused by a glutamine repeat expansion in huntingtin protein (HTT). Brain-specific knockout of Sirt1 results in exacerbation of brain pathology in a mouse model of Huntington's disease, whereas overexpression of Sirt1 improves survival, neuropathology and the expression of brain-derived neurotrophic factor (BDNF) in Huntington's disease mice. We show that Sirt1 deacetylase activity directly targets neurons to mediate neuroprotection from mutant HTT. The neuroprotective effect of Sirt1 requires the presence of CREB-regulated transcription coactivator 1 (TORC1), a brain-specific modulator of CREB activity. We show that under normal conditions, Sirt1 deacetylates and activates TORC1 by promoting its dephosphorylation and its interaction with CREB. We identified BDNF as a key target of Sirt1 and TORC1 transcriptional activity in both normal and Huntington's disease neurons. Mutant HTT interferes with the TORC1-CREB interaction to repress BDNF transcription, and Sirt1 rescues this defect in vitro and in vivo. These studies suggest a key role for Sirt1 in transcriptional networks in both the normal and Huntington's disease brain and offer an opportunity for therapeutic development.
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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.