Mechanisms of transcriptional dysregulation in Huntington's disease

Recent studies have provided strong evidence for transcription-related deficits in Huntington's disease (HD). These discoveries include consistent changes in steady-state mRNA levels, direct interactions between huntingtin and known transcription factor proteins, sequestration of transcription-related factors into polyglutamine aggregates, and inhibition of enzymes involved in chromatin remodeling. Also, there is increasing evidence that huntingtin itself may be a transcriptional regulator. This review discusses the cumulative body of evidence for transcriptional dysregulation as a mechanism of HD pathogenesis and possible implications for disease progression and treatment. (C) 2003 Elsevier B.V. All rights reserved.