Human Genome & Diseases: Review

Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 22, pp 2642-2660

First online:

Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies

  • M. Borrell-PagèsAffiliated withCNRS UMR 146, Institut CurieNeurovascular Research Laboratory, Vall d’Hebron Hospital, Universitat Autonoma de Barcelona
  • , D. ZalaAffiliated withCNRS UMR 146, Institut Curie
  • , S. HumbertAffiliated withCNRS UMR 146, Institut Curie Email author 
  • , F. SaudouAffiliated withCNRS UMR 146, Institut Curie Email author 

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Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin. Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to new therapeutic approaches.


CAG expansion polyglutamine aggregation intracellular transport transcription signal transduction therapy