Transcriptional dysregulation in Huntington鈥檚 disease: The role of histone deacetylases

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• 作者：Sorabh Sharma^a ; ^{sharmasorabh88@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Rajeev Taliyan^b
• 关键词：AD ; Alzheimer&rsquo ; s disease ; BDNF ; brain derived neurotrophic factor ; CBP ; CREB binding protein ; CREB ; cAMP response element binding protein ; GDNF ; glial-cell derived neurotrophic factor ; HD ; Huntington&rsquo ; s disease ; HDAC ; histone deacetylases ; HDACI ; histone deacetylases inhibitors ; HSP90 ; heat shock protein 90 ; Htt ; Huntingtin ; mhtt ; mutant huntingtin ; PD ; Parkinson&rsquo ; s disease ; SAHA ; suberoylanilide hydroxamic acid ; TSA ; trichostatin A
• 刊名：Pharmacological Research
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：100
• 期：Complete
• 页码：157-169
• 全文大小：1962 K

文摘

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.