ArticleHuman molecular genetics2014
The histone deacetylase HDAC3 is essential for Purkinje cell function, potentially complicating the use of HDAC inhibitors in SCA1.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Translational Relevance of SCA1 Models for the Development of Therapies for Spinocerebellar Ataxia Type 1.Biomedicines · 2025Review
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Upregulated spinal histone deacetylases induce nociceptive sensitization by inhibiting the GABA system in chronic constriction injury-induced neuropathy in rats.Pain reports · 2024Article
- Melatonin attenuates chronic sleep deprivation-induced cognitive deficits and HDAC3-Bmal1/clock interruption.CNS neuroscience & therapeutics · 2024Article
- Functional implications of paralog genes in polyglutamine spinocerebellar ataxias.Human genetics · 2023Review
- Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway.Journal of neuroinflammation · 2023Article
- Possible implication of miR-142-3p in coronary microembolization induced myocardial injury via ATXN1L/HDAC3/NOL3 axis.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Developmental Alterations in Adult-Onset Neurodegenerative Disorders: Lessons from Polyglutamine Diseases.Movement disorders : official journal of the Movement Disorder Society · 2021Article
- Ronin overexpression induces cerebellar degeneration in a mouse model of ataxia.Disease models & mechanisms · 2021Article
- Down-regulated HDAC3 elevates microRNA-495-3p to restrain epithelial-mesenchymal transition and oncogenicity of melanoma cells via reducing TRAF5.Journal of cellular and molecular medicine · 2020Article
- Article
- Gene Deregulation and Underlying Mechanisms in Spinocerebellar Ataxias With Polyglutamine Expansion.Frontiers in neuroscience · 2020Review
- The impact of histone post-translational modifications in neurodegenerative diseases.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Loss of the dystonia gene Thap1 leads to transcriptional deficits that converge on common pathogenic pathways in dystonic syndromes.Human molecular genetics · 2019Article
- Self-assembling vascular endothelial growth factor nanoparticles improve function in spinocerebellar ataxia type 1.Brain : a journal of neurology · 2019Article
- Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1.The Journal of clinical investigation · 2018Article
- Complex neuroprotective and neurotoxic effects of histone deacetylases.Journal of neurochemistry · 2018Review
- Tolerance of chronic HDACi treatment for neurological, visceral and lung Niemann-Pick Type C disease in mice.Scientific reports · 2018Article
- Transcriptional Dysregulation and Post-translational Modifications in Polyglutamine Diseases: From Pathogenesis to Potential Therapeutic Strategies.Frontiers in molecular neuroscience · 2018Review
- Age-related alterations in histone deacetylase expression in Purkinje neurons of ethanol-fed rats.Brain research · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Spinocerebellar ataxia type 1 (SCA1) is an incurable neurodegenerative disease caused by a pathogenic glutamine repeat expansion in the protein ataxin-1 (ATXN1). One likely mechanism mediating pathogenesis is excessive transcriptional repression induced by the expanded ATXN-1. Because ATXN1 binds HDAC3, a Class I histone deacetylase (HDAC) that we have found to be required for ATXN1-induced transcriptional repression, we tested whether genetically depleting HDAC3 improves the phenotype of the SCA1 knock-in mouse (SCA1(154Q/2Q)), the most physiologically relevant model of SCA1. Given that HDAC3 null mice are embryonic lethal, we used for our analyses a combination of HDAC3 haploinsufficient and Purkinje cell (PC)-specific HDAC3 null mice. Although deleting a single allele of HDAC3 in the context of SCA1 was insufficient to improve cerebellar and cognitive deficits of the disease, a complete loss of PC HDAC3 was highly deleterious both behaviorally, with mice showing early onset ataxia, and pathologically, with progressive histologic evidence of degeneration. Inhibition of HDAC3 may yet have a role in SCA1 therapy, but our study provides cautionary evidence that this approach could produce untoward effects. Indeed, the neurotoxic consequences of HDAC3 depletion could prove relevant, wherever pharmacologic inhibition of HDAC3 is being contemplated, in disorders ranging from cancer to neurodegeneration.
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