title: Histone deacetylase inhibitors as therapeutics for polyglutamine disorders.
abstract: During the past 5 years, gene expression studies in cell culture, animal models and in the brains of patients have shown that the perturbation of transcription frequently results in neuronal dysfunction in polyglutamine repeat diseases such as Huntington's disease. Histone deacetylases act as repressors of transcription through interactions with co-repressor complexes, which leads to chromatin remodelling. Aberrant interactions between polyglutamine proteins and regulators of transcription could be one mechanism by which transcriptional dysregulation occurs. Here, we discuss the potential therapeutic pathways through which histone deacetylase inhibitors might act to correct the aberrant transcription observed in Huntington's disease and other polyglutamine repeat diseases.
authors.affiliation: King's College London School of Medicine, Department of Medical and Molecular Genetics, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Butler
authors.forename: Gillian P
authors.initials: GP
authors.lastname: Bates
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D006816:Huntington Disease; D008954:Models, Biological; D020191:Myoclonic Epilepsies, Progressive; D010455:Peptides; D020754:Spinocerebellar Ataxias; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010455:Peptides; C097188:polyglutamine; D006655:Histone Deacetylases