Recent advances on the pathogenesis of Huntington's disease

Exp Neurol. 1999 May;157(1):1-18. doi: 10.1006/exnr.1998.7006.


We review recent advances regarding the pathogenesis of Huntington's disease (HD). This genetic neurodegenerative disorder is caused by an expanded CAG repeat in a gene coding for a protein, with unknown function, called huntingtin. There is selective death of striatal and cortical neurons. Both in patients and a transgenic mouse model of the disease, neuronal intranuclear inclusions, immunoreactive for huntingtin and ubiquitin, develop. Huntingtin interacts with the proteins GAPDH, HAP-1, HIP1, HIP2, and calmodulin, and a mutant huntingtin is specifically cleaved by the proapoptotic enzyme caspase 3. The pathogenetic mechanism is not known, but it is presumed that there is a toxic gain of function of the mutant huntingtin. Circumstantial evidence suggests that excitotoxicity, oxidative stress, impaired energy metabolism, and apoptosis play a role.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Huntington Disease / epidemiology
  • Huntington Disease / etiology*
  • Huntington Disease / genetics
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Models, Neurological
  • Neurology / trends*