A microRNA-based gene dysregulation pathway in Huntington's disease

Neurobiol Dis. 2008 Mar;29(3):438-45. doi: 10.1016/j.nbd.2007.11.001. Epub 2007 Nov 13.


Huntington's disease (HD) is a dominantly-inherited neurodegenerative disorder which is incurable and ultimately fatal. HD is characterised by widespread mRNA dysregulation, particularly in neurons of the forebrain, by mechanisms which are not fully understood. Such dysregulation has been demonstrated to result, in part, from aberrant nuclear localisation of the transcriptional repressor, REST. Here, we show that expression of a number of neuronal-specific microRNAs is also dysregulated in HD tissues, probably as a result of increased repression by REST. This phenomenon is observed in both murine models of HD and in the brains of human HD sufferers. MicroRNA loss is reflected in increased levels of a number of target messenger RNAs. These data are the first to demonstrate a role for microRNAs in HD, and indicate that the molecular aetiology of HD is reflected in a loss of neuronal identity, caused in part by dysregulation of both transcriptional and post-transcriptional mechanisms.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / pathology
  • Brain / physiology
  • Cells, Cultured
  • Gene Targeting / methods
  • Humans
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • Mice
  • Mice, Transgenic
  • MicroRNAs / physiology*
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics
  • Signal Transduction / genetics*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics


  • MicroRNAs
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Transcription Factors