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- Title
Mutant protein in Huntington disease is resistant to proteolysis in affected brain.
- Authors
Dyer, Roy B.; McMurray, Cynthia T.
- Abstract
The cause of Huntington disease pathophysiology is unknown, but a major hypothesis suggests that toxicity arises from the cleavage and accumulation of amino-terminal fragments containing an expanded polyglutamine region. In evaluating huntingtin protein (HD) from human brain, transgenic animals and cells, we observed, unexpectedly, that mutant HD is more resistant to proteolysis than normal HD. The N-terminal cleavage fragments we observed arise from the processing of normal HD and are sequestered by full-length mutant HD. Our results support a model in which inhibition of proteolysis of mutant HD leads to aggregation and toxicity through the sequestering of important targets, including normal HD.
- Subjects
HUNTINGTON disease; PATHOLOGICAL physiology
- Publication
Nature Genetics, 2001, Vol 29, Issue 3, p270
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng745