Journal
JOURNAL OF MOLECULAR MEDICINE-JMM
Volume 85, Issue 12, Pages 1421-1428Publisher
SPRINGER
DOI: 10.1007/s00109-007-0251-9
Keywords
celastrol; HSF1; polyglutamine; aggregates; heat shock proteins; hsp70
Funding
- NIGMS NIH HHS [R01 GM061053, R01 GM064606, GM61053, GM64606] Funding Source: Medline
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Heat shock proteins (hsps) are protective against the harmful effects of mutant expanded polyglutamine repeat proteins that occur in diseases such as Huntington's, prompting the search for pharmacologic compounds that increase hsp expression in cells as potential treatments for this and related diseases. In this paper, we show that celastrol, a compound recently shown to up-regulate hsp gene expression, significantly decreases killing of cells expressing mutant polyglutamine protein. This effect requires the presence of the transcription factor responsible for mediating inducible hsp gene expression, HSF1, and is correlated with decreased amounts and increased sodium dodecyl sulfate (SDS) solubility of polyglutamine aggregates. These results suggest the potential of celastrol as a therapeutic agent in the treatment of human polyglutamine expansion diseases.
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