Aggregation of expanded huntingtin in the brains of patients with Huntington disease

Prion. Jan-Mar 2007;1(1):26-31. doi: 10.4161/pri.1.1.4056.

Abstract

Huntingtin containing an expanded polyglutamine causes neuronal death and Huntington disease. Although expanded huntingtin is found in virtually every cell type, its toxicity is limited to neurons of certain areas of the brain, such as cortex and caudate/putamen. In affected areas of the brain, expanded huntingtin is not found in its intact monomeric form. It is found instead in the form of N-terminal fragments, oligomers and polymers, all of which accumulate in the cortex. Whereas the oligomer is mostly soluble, the polymers and the fragments associate with each other and with other proteins to form the insoluble inclusions characteristic of the disease. It is likely that the aggregates containing expanded huntingtin are toxic to neurons, but it remains to be determined whether the oligomer or the inclusion is the toxic species.

Publication types

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

MeSH terms

  • Brain Chemistry*
  • Cell Death
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Humans
  • Huntingtin Protein
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / pathology
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Peptides / chemistry
  • Peptides / metabolism*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Peptides
  • polyglutamine