Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease.

ABSTRACT: Huntington disease (HD) is a devastating neurodegenerative disorder for which there are no disease-modifying treatments. Previous studies have proposed that activation of the heat shock response (HSR) via the transcription factor heat shock factor 1 (HSF1) may be of therapeutic benefit. However, the effect of disease progression on the HSR and the therapeutic potential of this pathway are currently unknown. Here, we used a brain-penetrating HSP90 inhibitor and physiological, molecular, and behavioral readouts to demonstrate that pharmacological activation of HSF1 improves huntingtin aggregate load, motor performance, and other HD-related phenotypes in the R6/2 mouse model of HD. However, the beneficial effects of this treatment were transient and diminished with disease progression. Molecu

SUBMITTER: Labbadia J 

PROVIDER: S-EPMC3148745 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature