ArticleNature medicine2011
Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 189 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
189 citing papers in PubMed, 1 synthesis or guideline pooled it, 344 citations in OpenAlex.
- Sirtuin Acetylation and Deacetylation: a Complex Paradigm in Neurodegenerative Disease.Molecular neurobiology · 2021Pooled it
- An exploratory double-blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington's disease.British journal of clinical pharmacology · 2015Trial
- 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
- Intermediate leucine catabolism is associated with longevity and sustained reproduction in grasshoppers.GeroScience · 2026Article
- Review
- Grape Seed Extract as an Adjuvant Therapy for Huntington Disease; A Narrative Review of Biological Plausibility and Potential Clinical Outcomes.Molecules (Basel, Switzerland) · 2026Review
- Bioactive Phytochemicals in Experimental Models of Multiple Sclerosis: Mechanisms, Efficacy, and Translational Potential.Nutrients · 2026Review
- Identification of enzymatically modified isoquercitrin as a therapeutic lead for myotonic dystrophy type 1.NAR molecular medicine · 2026Article
- Sirtuins as Therapeutic Targets for Treating Cancer, Metabolic Diseases, and Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Antioxidant and Anti-Inflammatory Defenses in Huntington's Disease: Roles of NRF2 and PGC-1α, and Therapeutic Strategies.Life (Basel, Switzerland) · 2025Review
- Unravelling Convergent Signaling Mechanisms Underlying the Aging-Disease Nexus Using Computational Language Analysis.Current issues in molecular biology · 2025Article
- Ubiquitin specific peptidase 11 knockdown slows Huntington's disease progression via regulating mitochondrial dysfunction and neuronal damage depending on PTEN-mediated AKT pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Ferulic acid mitigates 3-Nitropropionic acid-induced Huntington's disease via modulation of Nrf2/HO-1, TLR4/NF-κB, and SIRT1/p53 signaling pathways.Frontiers in pharmacology · 2025Article
- Circadian Rhythms and Lung Cancer in the Context of Aging: A Review of Current Evidence.Aging and disease · 2025Review
- Interaction between resveratrol and SIRT1: role in neurodegenerative diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Current aspects of targeting cellular senescence for the therapy of neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy.Brain : a journal of neurology · 2024Article
- Mitochondrial targeted antioxidants as potential therapy for huntington's disease.Pharmacological reports : PR · 2024Review
- Dietary fasting and time-restricted eating in Huntington's disease: therapeutic potential and underlying mechanisms.Translational neurodegeneration · 2024Review
129 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
30 authors at 10 institutions in 3 countries.
Funding
Abstract
Huntington's disease is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in huntingtin (HTT) protein. We previously showed that calorie restriction ameliorated Huntington's disease pathogenesis and slowed disease progression in mice that model Huntington's disease (Huntington's disease mice). We now report that overexpression of sirtuin 1 (Sirt1), a mediator of the beneficial metabolic effects of calorie restriction, protects neurons against mutant HTT toxicity, whereas reduction of Sirt1 exacerbates mutant HTT toxicity. Overexpression of Sirt1 improves motor function, reduces brain atrophy and attenuates mutant-HTT-mediated metabolic abnormalities in Huntington's disease mice. Further mechanistic studies suggested that Sirt1 prevents the mutant-HTT-induced decline in brain-derived neurotrophic factor (BDNF) concentrations and the signaling of its receptor, TrkB, and restores dopamine- and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) concentrations in the striatum. Sirt1 deacetylase activity is required for Sirt1-mediated neuroprotection in Huntington's disease cell models. Notably, we show that mutant HTT interacts with Sirt1 and inhibits Sirt1 deacetylase activity, which results in hyperacetylation of Sirt1 substrates such as forkhead box O3A (Foxo3a), thereby inhibiting its pro-survival function. Overexpression of Sirt1 counteracts the mutant-HTT-induced deacetylase deficit, enhances the deacetylation of Foxo3a and facilitates cell survival. These findings show a neuroprotective role for Sirt1 in mammalian Huntington's disease models and open new avenues for the development of neuroprotective strategies in Huntington's disease.
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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.