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Current Trends in Neurology   Volumes    Volume 4 
Abstract
Histone deacetylase inhibitors as therapeutic targets for muscular dystrophy
Hiroki Hagiwara, Ayami Nakamura, Kiichiro Matsumura
Pages: 71 - 80
Number of pages: 10
Current Trends in Neurology
Volume 4 

Copyright © 2010 Research Trends. All rights reserved

ABSTRACT
 
Epigenetic mechanisms attract attention as the main driving force for critical changes in gene expression without changes in DNA sequence. Above all, histone acetylation has been extensively characterized and shown to be fundamental for transcriptional regulation. High levels of histone acetylation are correlated with gene activation, while deacetylation of histones corresponds with gene repression. It has been demonstrated that deacetylation of histones play crucial roles in progression of not only diverse carcinomas but also neuromuscular disorders. Histone deacetylase inhibitors (HDACIs) represent a new and promising class of drugs that promote gene expression by enhancing acetylation of histones in specific chromatin domains. Indeed, several HDACIs are already in clinical trials for the treatment of various diseases such as cancers and spinal muscular atrophy. Muscular dystrophies, including the most common and devastating form Duchenne muscular dystrophy, are groups of inherited myogenic disorders characterized by progressive muscle wasting and weakness of variable distribution and severity. Although significant effort has been paid for the development of effective treatments for muscular dystrophies, there are thus far no established effective therapeutic approaches for these diseases. Recently, HDACIs were shown to promote recovery of dystrophic muscles in a mouse model of muscular dystrophies. Therefore, HDACIs are expected to be one of the most promising treatments for muscular dystrophies. In this review, we discuss new insights into the molecular mechanism of HDACIs therapeutics, their current status of clinical development and possible future use in the treatment of muscular dystrophies.
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