Sci. Aging Knowl. Environ., 17 September 2003
Vol. 2003, Issue 37, p. pe26
[DOI: 10.1126/sageke.2003.37.pe26]


How Does the Huntington's Disease Mutation Damage Cells?

David C. Rubinsztein

The author is in the Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK. E-mail: dcr1000{at};2003/37/pe26

Key Words: polyglutamine expansion • huntingtin • neurodegeneration • Huntington's disease

Abstract: Huntington's Disease (HD) is an autosomal dominant neurodegenerative condition with devastating consequences. HD is caused by the expansion of a CAG trinucleotide repeat stretch in the coding sequence of the HD gene that gives rise to a long polyglutamine tract in the huntingtin protein. How this mutated protein gives rise to the disease state is controversial. In this Perspective, I discuss the results of a new study on the effects of the mutated huntingtin protein in light of previous findings and suggest that the HD mutation damages cells by perturbing multiple parallel pathways by gain-of-function and possibly also dominant negative mechanisms.

Citation: D. C. Rubinsztein, How Does the Huntington's Disease Mutation Damage Cells? Sci. SAGE KE 2003 (37), pe26 (2003).

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