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Heat shock response modulators as therapeutic tools for diseases of protein conformation

Sandy D Westerheide1, Richard I Morimoto

  • 1Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208, USA.

The Journal of Biological Chemistry
|August 4, 2005
PubMed

Insights

Disrupted protein folding quality control causes toxic protein aggregation in neurodegenerative diseases. Enhancing molecular chaperones via heat shock transcription factor 1 (HSF1) may restore cellular function and offer therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Pharmacology

Background:

  • Disrupted protein folding quality control leads to the accumulation of misfolded proteins, forming aggregates implicated in neurodegenerative diseases.
  • Over 100 human diseases share the common feature of unstable, self-associating off-pathway folding intermediates, causing chronic protein homeostasis imbalance and cellular dysfunction.

Purpose of the Study:

  • To review the regulation of molecular chaperones and protein homeostasis by heat shock transcription factor 1 (HSF1).
  • To explore small molecule regulators of the heat shock response as a therapeutic strategy for protein conformational diseases.

Main Methods:

  • Literature review focusing on heat shock transcription factor 1 (HSF1) and its role in protein homeostasis.
  • Analysis of current research on small molecule modulators of the heat shock response.

Main Results:

  • HSF1 is identified as the master stress-inducible regulator of molecular chaperones and protein homeostasis.
  • Pharmacological activation of the heat shock response shows potential for therapeutic intervention in protein conformational diseases.

Conclusions:

  • Enhancing molecular chaperone levels and activity, regulated by HSF1, can suppress protein aggregation and toxicity.
  • Targeting the heat shock response with small molecules presents a promising therapeutic avenue for treating diseases of protein misfolding.

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