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Transcriptional dysregulation in Huntington's disease: The role of histone deacetylases.

Abstract
Huntington's disease (HD) is a progressive neurological disorder for which there are no disease-modifying treatments. Although, the exact underlying mechanism(s) leading to the neural cell death in HD still remains elusive, the transcriptional dysregulation is a major molecular feature. Recently, the transcriptional activation and repression regulated by chromatin acetylation has been found to be impaired in HD pathology. The acetylation and deacetylation of histone proteins is carried out by opposing actions of histone acetyl-transferases and histone deacetylases (HDACs), respectively. Studies carried out in cell culture, yeast, Drosophila and rodent model(s) have indicated that HDAC inhibitors (HDACIs) might provide useful class of therapeutic agents for HD. Clinical trials have also reported the beneficial effects of HDACIs in patients suffering from HD. Therefore, the development of HDACIs as therapeutics for HD has been vigorously pursued. In this review, we highlight and summarize the putative role of HDACs in HD like pathology and further discuss the potential of HDACIs as new therapeutic avenues for the treatment of HD.
AuthorsSorabh Sharma, Rajeev Taliyan
JournalPharmacological research (Pharmacol Res) Vol. 100 Pg. 157-69 (Oct 2015) ISSN: 1096-1186 [Electronic] Netherlands
PMID26254871 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
Topics
  • Animals
  • Histone Deacetylase Inhibitors (pharmacology, therapeutic use)
  • Histone Deacetylases (genetics)
  • Humans
  • Huntington Disease (drug therapy, genetics)
  • Transcription, Genetic (drug effects, genetics)

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