Authors: Sadri-Vakili, Ghazaleh; Cha, Jang-Ho J.

Source: Current Alzheimer Research, Volume 3, Number 4, September 2006 , pp. 403-408(6)

Publisher: Bentham Science Publishers

Abstract:

Huntington's disease is an autosomal dominantly inherited neurodegenerative disorder caused by a polyglutamine repeat expansion. The onset of HD leads to problems with movement, cognition, and behavioral functioning and there is currently no effective treatment. The mechanism by which mutant huntingtin causes neuronal dysfunction is not known. However, multiple pathologic mechanisms have been discovered. Recent studies provide strong evidence for transcriptional dysregulation as a mechanism of HD pathogenesis. The control of eukaryotic gene expression depends on the modification of histone proteins associated with specific genes; acetylation and deacetylation of histones play a critical role in gene expression. Studies in numerous HD models have shown that mutant huntingtin expression leads to a change in histone acetyl transferase (HAT) activity and suggest that aberrant HAT activity may be an underlying mechanism of transcriptional dysregulation in HD. Furthermore, recent studies have shown a therapeutic role for histone deacetylase (HDAC) inhibitors in a number of HD models. In this review we discuss a number of studies that use HDAC inhibitors as therapeutic agents in HD models. These studies demonstrate that HDAC inhibitors are a promising therapeutic approach for the treatment of HD.

Keywords: IT15 gene; CREB binding protein (CBP); Chromatin remodeling; genetic mutation; Htt sequester proteins

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156720506778249407

Affiliations: 1: Massachusetts General Hospital,MassGeneral Institute for Neurodegenerative Disease, 114 16th Street/B114-2001, Charlestown, MA 02129-4404, USA.

Publication date: 2006-09-01

More about this publication?

• Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

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