Histone deacetylase inhibitors as therapeutic agents for polyglutamine disorders / 中华医学遗传学杂志

ABSTRACT

During the past few years, gene expression studies have shown that the perturbation of transcription frequently results in neuronal dysfunction in polyglutamine (PolyQ) diseases such as Huntington's disease (HD). Histone deacetylases (HDACs) act as repressors of transcription through interaction with co-repressor complexes, leading to chromatin remodelling. Aberrant interaction between PolyQ proteins and regulators of transcription could be one mechanism by which transcriptional dysregulation occurs. Here, the authors discuss the possible mechanism of transcriptional dysfunction in PolyQ disease, including the effect of histone acetyltransferases (HATs) and HDACs on pathogenesis, and the potential therapeutic pathways through which histone deacetylase inhibitors (HDACIs) might act to correct the aberrant transcription observed in HD and other PolyQ diseases.