| Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders? | |
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MedLine Citation:
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PMID: 19917878 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In recent years, it has become widely recognized that a comprehensive understanding of chromatin biology is necessary to better appreciate its role in a wide range of diseases. The histone code has developed as a new layer of our appreciation of transcription factor-based mechanisms of gene expression. Although epigenetic regulation refers to a host of chromatin modifications that occur at the level of DNA, histones, and histone-associated proteins, how this regulation is orchestrated is still incompletely understood. Of those processes that comprise the epigenetic regulatory machinery, DNA methylation and histone acetylation/deacetylation have been the most thoroughly studied. Compounds that act as inhibitors of DNA methyltransferases or histone deacetylases (HDACs) activate a variety of intracellular signaling pathways that ultimately affect the coordinated expression of multiple genes. The altered patterns of mRNA and protein expression collectively converge on pathways linked to apoptosis and cell cycle arrest, among others. This has prompted a widespread search for epigenetic inhibitors that could be used as chemotherapeutic agents, and several are undergoing clinical evaluation. More recently, there has been interest in the use of HDAC inhibitors to activate the expression of mRNAs that are down-regulated in various neurological and psychiatric conditions. Considerably less is known regarding the effect these drugs have on postmitotic cells such as neurons. Before we consider the clinical use of additional HDAC inhibitors to treat schizophrenia or unipolar depression, there are a number of key issues that need to be resolved. |
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Authors:
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Dennis R Grayson; Marija Kundakovic; Rajiv P Sharma |
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Publication Detail:
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Type: Journal Article; Review Date: 2009-11-16 |
Journal Detail:
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Title: Molecular pharmacology Volume: 77 ISSN: 1521-0111 ISO Abbreviation: Mol. Pharmacol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-20 Completed Date: 2010-02-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0035623 Medline TA: Mol Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 126-35 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, University of Illinois, Chicago, IL 60612, USA. dgrayson@psych.uic.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Forecasting Gene Expression Regulation / drug effects Histone Deacetylase Inhibitors / chemistry, therapeutic use* Histone Deacetylases / genetics, metabolism Humans Mental Disorders / drug therapy*, enzymology, genetics |
| Chemical | |
Reg. No./Substance:
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0/Histone Deacetylase Inhibitors; EC 3.5.1.98/Histone Deacetylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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