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

J Biol Chem. 2013 Aug 16;288(33):23633-8. doi: 10.1074/jbc.C113.481945. Epub 2013 Jul 9.


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 in cells expressing aggregation-prone, polyglutamine-expanded fragments of HTT. These data suggest that the HSR does not mitigate inclusion body formation.

Keywords: Flow Cytometry; Heat Shock Protein; Heat Shock Response; Huntington Disease; Molecular Chaperone; Protein Aggregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / metabolism
  • HEK293 Cells
  • Heat Shock Transcription Factors
  • Heat-Shock Response*
  • Humans
  • Huntington Disease / metabolism*
  • Huntington Disease / pathology
  • Inclusion Bodies / metabolism*
  • Models, Biological*
  • Mutant Proteins / metabolism
  • Protein Binding
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Mutant Proteins
  • Transcription Factors