Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model
Language: 
English
Abstract: 

In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expanded huntingtin exon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates. Clioquinol treatment of transgenic Huntington's mice (R6/2) improved behavioral and pathologic phenotypes, including decreased huntingtin aggregate accumulation, decreased striatal atrophy, improved rotarod performance, reduction of weight loss, normalization of blood glucose and insulin levels, and extension of lifespan. Our results suggest that clioquinol is a candidate therapy for Huntington's disease and other polyglutamine-expansion diseases.

Author(s): 
Nguyen, Trent
Hamby, Aaron
Massa, Stephen M.
Item Type: 
Journal Article
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation: 
Proc. Natl. Acad. Sci. U.S.A.
Publication Date: 
8/16/2005
Publication Year: 
2005
Pages: 
11840-11845
Volume: 
102
Issue: 
33
ISSN: 
0027-8424
DOI: 
10.1073/pnas.0502177102
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 16087879 PMCID: PMC1187967

Turabian/Chicago Citation

Trent Nguyen, Aaron Hamby and Stephen M. Massa. 8/16/2005. "Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model." Proceedings of the National Academy of Sciences of the United States of America 102: 33: 11840-11845. 10.1073/pnas.0502177102.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1073/pnas.0502177102 | issn = 0027-8424 | volume = 102 | pages = 11840-11845 | last = Nguyen | first = Trent | coauthors = Hamby, Aaron, Massa, Stephen M. | title = Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model | journal = Proceedings of the National Academy of Sciences of the United States of America | date = 8/16/2005 | pmid = | pmc = }} </ref>