Fig. 3
From: The heat shock response in neurons and astroglia and its role in neurodegenerative diseases
Proposed summary of changes in the HSR and its components in polyQ-expanded Htt over-expression models of HD. Huntington’s disease onset and progression into late stage is dependent on the molecular pathologies developed in striatal neurons (e.g. formation of polyQ-expanded Htt aggregates or IPODs) and astroglia (e.g. decline in GLAST/GLT-1 expression and the secretion of unidentified toxic “factors”). The susceptibility of striatal neurons to degeneration from HD-associated stresses could be the result of a polyQ-expanded Htt-mediated attenuation of the HSR. Over-expression of polyQ-expanded Htt in CNS tissues results in a (1) reduction in HSF1 levels. (2) Histone H4 acetylation has been shown to be a strong promoter of HSF1 binding to DNA of target genes. However, hypoacetylation of histone H4 at HSF1 targets (e.g. Hspa1b, Hspb1, and Dnajb1) with disease progression can explain (3) the decrease in HSF1 binding to DNA observed in polyQ-expanded Htt expressing striatal neurons. (4) HD disease progression is also associated with a decline in Hsp70 and Hsp40 family members and (5) a striatal-specific increase in Hsp60. (6) There have been few investigations regarding HSF1 activation and DNA-binding in astroglia. Therefore, the capacity of polyQ-expanded Htt over-expressing astroglia to activate HSF1 and induce an HSR is currently unknown