ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
SIRT1 modulates aggregation and toxicity through deacetylation of the androgen receptor in cell models of SBMA.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 71 citations in OpenAlex.
- Delactylase effects of SIRT1 on a positive feedback loop involving the H19-glycolysis-histone lactylation in gastric cancer.Oncogene · 2025Article
- SIRT1: potential target in glucocorticoid-resistant diseases.Frontiers in immunology · 2025Review
- Differentially disrupted spinal cord and muscle energy metabolism in spinal and bulbar muscular atrophy.JCI insight · 2024Article
- Article
- Bicalutamide and Trehalose Ameliorate Spinal and Bulbar Muscular Atrophy Pathology in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- The role of ubiquitination in spinal and bulbar muscular atrophy.Frontiers in molecular neuroscience · 2022Review
- A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases.Frontiers in molecular neuroscience · 2022Review
- Exploring the Role of Posttranslational Modifications in Spinal and Bulbar Muscular Atrophy.Frontiers in molecular neuroscience · 2022Review
- KAT2A-mediated AR translocation into nucleus promotes abiraterone-resistance in castration-resistant prostate cancer.Cell death & disease · 2021Article
- Deubiquitinase USP7 contributes to the pathogenicity of spinal and bulbar muscular atrophy.The Journal of clinical investigation · 2021Article
- SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan.Current neuropharmacology · 2021Review
- Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer.Asian journal of urology · 2020Review
- The Role of Sex and Sex Hormones in Neurodegenerative Diseases.Endocrine reviews · 2020Review
- Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.Journal of the Endocrine Society · 2019Article
- Impaired Nuclear Export of Polyglutamine-Expanded Androgen Receptor in Spinal and Bulbar Muscular Atrophy.Scientific reports · 2019Article
- Autophagic and Proteasomal Mediated Removal of Mutant Androgen Receptor in Muscle Models of Spinal and Bulbar Muscular Atrophy.Frontiers in endocrinology · 2019Article
- SIRT1 deacetylase in aging-induced neuromuscular degeneration and amyotrophic lateral sclerosis.Aging cell · 2018Article
- Transcriptional Dysregulation and Post-translational Modifications in Polyglutamine Diseases: From Pathogenesis to Potential Therapeutic Strategies.Frontiers in molecular neuroscience · 2018Review
- Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Posttranslational protein modifications can play a major role in disease pathogenesis; phosphorylation, sumoylation, and acetylation modulate the toxicity of a variety of proteotoxic proteins. The androgen receptor (AR) is substantially modified, in response to hormone binding, by phosphorylation, sumoylation, and acetylation; these modifications might thus contribute to DHT-dependent polyglutamine (polyQ)-expanded AR proteotoxicity in spinal and bulbar muscular atrophy (SBMA). SIRT1, a nuclear protein and deacetylase of the AR, is neuroprotective in many neurodegenerative disease models. Our studies reveal that SIRT1 also offers protection against polyQ-expanded AR by deacetylating the AR at lysines 630/632/633. This finding suggested that nuclear AR acetylation plays a role in the aberrant metabolism and toxicity of polyQ-expanded AR. Subsequent studies revealed that the polyQ-expanded AR is hyperacetylated and that pharmacologic reduction of acetylation reduces mutant AR aggregation. Moreover, genetic mutation to inhibit polyQ-expanded AR acetylation of lysines 630/632/633 substantially decreased its aggregation and completely abrogated its toxicity in cell lines and motor neurons. Our studies also reveal one means by which the AR acetylation state likely modifies polyQ-expanded AR metabolism and toxicity, through its effect on DHT-dependent AR stabilization. Overall, our findings reveal a neuroprotective function of SIRT1 that operates through its deacetylation of polyQ-expanded AR and highlight the potential of both SIRT1 and AR acetylation as powerful therapeutic targets in SBMA.
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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.