Heat shock response activation exacerbates inclusion body formation in a cellular model of Huntington’s disease.

701

Abstract

The cellular heat shock response (HSR) protects cells from toxicity associated with defective protein folding and this pathway is widely viewed as a potential pharmacological target to treat neurodegenerative diseases linked to protein aggregation. Here we show that the HSR is not activated by mutant huntingtin (htt) even in cells selected for the highest expression levels and for the presence of inclusion bodies containing aggregated protein. Surprisingly, HSR activation by HSF1 overexpression or by administration of a small molecule activator lowers the concentration threshold at which htt forms inclusion bodies (IB) in cells expressing aggregation-prone, polyglutamine expanded fragments of htt. These data suggest that the HSR does not mitigate IB formation.

FREE FULL TEXT PDF 

FREE FULL TEXT HTML 

Source: jbc.org

 



Copyright: All rights of any text or trademarks mentioned in the article are reserved to their respective owners.

AICH ROMA ONLUS