Histone deacetylases as targets for the treatment of human neurodegenerative diseases.
Histone deacetylases (HDACs) are a family of proteins that play an important role in regulating transcription as well as the function of a variety of cellular proteins. While these proteins are expressed abundantly in the brain, little is known about their roles in brain function. A growing body of evidence suggests that HDACs regulate neuronal survival. Results from studies conducted in vertebrate and mammalian experimental systems indicate that while some of these proteins are involved in promoting neuronal death, a majority of the HDACs studied thus far protect against neurodegeneration. Here we review the research performed on the role played by individual members of the HDAC family in the regulation of neuronal death. Chemical inhibitors of HDACs have been used in a variety of models of neurodegenerative disorders. We summarize the results from these studies, which indicate that HDAC inhibitors show great promise as therapeutic agents for human neurodegenerative disorders.
D'Mello
Santosh R
SR
Department of Molecular and Cell Biology, University of Texas, Dallas, Texas, USA. dmello@utdallas.edu
D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome
D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D018696:Neuroprotective Agents; D037761:Sirtuins; D006655:Histone Deacetylases