Transcriptional dysregulation in Huntington's disease: A failure of adaptive transcriptional homeostasis Review uri icon

Overview

MeSH Major

  • Homeostasis
  • Huntington Disease
  • Transcription, Genetic

abstract

  • Huntington's disease (HD) is a signature polyglutamine disorder. An enduring theory of HD pathogenesis has involved dysregulation of transcription. Indeed, transcriptional regulatory proteins can be modulated to overcome cardinal features of HD-modeled mice, and efforts to move these into human studies are ongoing. Here, we discuss a unifying hypothesis emerging from these studies, which is that HD represents the pathological disruption of evolutionarily conserved adaptive gene programs to counteract oxidative stress, mitochondrial dysfunction and accumulation of misfolded proteins. Transcriptional dyshomeostasis of adaptive genes is further exacerbated by repression of genes involved in normal synaptic activity or growth factor signaling.

publication date

  • January 2014

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC4082751

Digital Object Identifier (DOI)

  • 10.1016/j.drudis.2014.03.016

PubMed ID

  • 24662036

Additional Document Info

start page

  • 956

end page

  • 62

volume

  • 19

number

  • 7