ArticlePloS one2012
Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- HDAC3 as an Emerging Therapeutic Target for Alzheimer's Disease and other Neurological Disorders.Molecular neurobiology · 2025Review
- HAT and HDAC: Enzyme with Contradictory Action in Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder.American journal of human genetics · 2024Article
- IndiSPENsable for X Chromosome Inactivation and Gene Silencing.Epigenomes · 2023Review
- A comparison of four technologies for detecting p53 aggregates in ovarian cancer.Frontiers in oncology · 2022Article
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
- Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington's Disease.ACS medicinal chemistry letters · 2021Article
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- Histone deacetylase-3: Friend and foe of the brain.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Epigenetic mechanisms of neurodegenerative diseases and acute brain injury.Neurochemistry international · 2020Review
- Complex neuroprotective and neurotoxic effects of histone deacetylases.Journal of neurochemistry · 2018Review
- A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington's disease mice.Scientific reports · 2017Article
- Contribution of Neuroepigenetics to Huntington's Disease.Frontiers in human neuroscience · 2017Review
- LBH589, A Hydroxamic Acid-Derived HDAC Inhibitor, is Neuroprotective in Mouse Models of Huntington's Disease.Journal of Huntington's disease · 2016Article
- Epigenetic Changes in Neurodegenerative Diseases.Molecules and cells · 2016Review
- The level and distribution pattern of HP1β in the embryonic brain correspond to those of H3K9me1/me2 but not of H3K9me3.Histochemistry and cell biology · 2016Article
- The Effects of Pharmacological Inhibition of Histone Deacetylase 3 (HDAC3) in Huntington's Disease Mice.PloS one · 2016Article
- The promise and perils of HDAC inhibitors in neurodegeneration.Annals of clinical and translational neurology · 2015Review
- Targets for future clinical trials in Huntington's disease: what's in the pipeline?Movement disorders : official journal of the Movement Disorder Society · 2014Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by an expansion of a CAG/polyglutamine repeat for which there are no disease modifying treatments. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression and has been recapitulated across multiple HD models. Altered histone acetylation has been proposed to underlie this transcriptional dysregulation and histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA), have been shown to improve polyglutamine-dependent phenotypes in numerous HD models. However potent pan-HDAC inhibitors such as SAHA display toxic side-effects. To better understand the mechanism underlying this potential therapeutic benefit and to dissociate the beneficial and toxic effects of SAHA, we set out to identify the specific HDAC(s) involved in this process. For this purpose, we are exploring the effect of the genetic reduction of specific HDACs on HD-related phenotypes in the R6/2 mouse model of HD. The study presented here focuses on HDAC3, which, as a class I HDAC, is one of the preferred targets of SAHA and is directly involved in histone deacetylation. To evaluate a potential benefit of Hdac3 genetic reduction in R6/2, we generated a mouse carrying a critical deletion in the Hdac3 gene. We confirmed that the complete knock-out of Hdac3 is embryonic lethal. To test the effects of HDAC3 inhibition, we used Hdac3(+/-) heterozygotes to reduce nuclear HDAC3 levels in R6/2 mice. We found that Hdac3 knock-down does not ameliorate physiological or behavioural phenotypes and has no effect on molecular changes including dysregulated transcripts. We conclude that HDAC3 should not be considered as the major mediator of the beneficial effect induced by SAHA and other HDAC inhibitors in HD.
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