, Volume 5, Issue 1, pp 9–17 | Cite as

Genetic and environmental factors in the pathogenesis of Huntington’s disease

  • Anton van DellenEmail author
  • Anthony J. Hannan
Review Article


Huntington’s disease is a fatal inherited disorder in which there is progressive neurodegeneration in specific brain areas, mainly the striatum and cerebral cortex, producing motor, cognitive, and psychiatric symptoms. The trinucleotide repeat mutation involved is common to many other brain diseases, which may therefore involve similar mechanisms of pathogenesis. We are beginning to understand how a CAG trinucleotide repeat expansion in the disease gene, encoding an expanded polyglutamine tract, induces neuronal dysfunction and symptomatology in Huntington’s disease. Recent evidence that environmental factors modify the onset and progression of neurodegeneration has shed new light on Huntington’s disease and other devastating brain diseases. This review focuses on genetic mediators, environmental modulators, and associated gene-environment interactions in the pathogenesis of Huntington’s disease.


Huntington’s disease CAG trinucleotide repeat expansion Neurodegeneration Environmental and genetic modulators Polyglutamine 



We are indebted to Tara Spires, Nektarios Mazarakis, Helen Grote, and Colin Blakemore for their contributions to the research described in this article. We also thank Carolyn Hannan, Monique Howard, and Caitlin McOmish for comments on the manuscript. The author’s research has been supported by the Rhodes Trust (A.D.), NHMRC (A.J.H.), Oxford Nuffield Medical Trust (A.J.H.), Royal Society, MRC (UK), and Wellcome Trust (A.J.H.).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.University Laboratory of PhysiologyUniversity of OxfordOxfordUK
  2. 2.Howard Florey InstituteUniversity of MelbourneAustralia

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