The role of immunity in Huntington's disease

Mol Psychiatry. 2011 Sep;16(9):889-902. doi: 10.1038/mp.2011.28. Epub 2011 Apr 26.


Huntington's disease (HD) is a devastating and incurable neurodegenerative disorder characterized by progressive cognitive, psychiatric and motor impairments. Although the disease has been seen as a disorder purely of the brain, there is now emerging evidence that abnormalities outside the central nervous system are commonly seen in HD. Indeed, the mutant huntingtin (mHtt) coded for by the abnormal gene in HD is found in every cell type where its presence has been sought. In particular, there are a number of recent observations in HD patients that mHtt interacts with the immune system with accumulating evidence that changes in the immune system may critically contribute to the pathology of HD. However, the nature of this contribution remains unclear, to the extent that it is not even known whether the immune system has a beneficial or detrimental role in HD patients. In this review, we attempt to bring a novel understanding to the interaction of the immune system to HD pathology, thereby shedding light on its potential pathogenic role. As part of this discussion, we revisit the clinical data on the anti-inflammatory drug trials in HD and propose new experimental approaches to interrogate the role of immunity in this currently incurable disorder.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Humans
  • Huntingtin Protein
  • Huntington Disease / complications
  • Huntington Disease / drug therapy
  • Huntington Disease / genetics
  • Huntington Disease / immunology*
  • Immune System Diseases / complications
  • Immune System Diseases / genetics
  • Immune System Diseases / psychology*
  • Immunity / genetics*
  • Inflammation / metabolism
  • Models, Immunological
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism


  • Anti-Inflammatory Agents
  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins