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

Sandy D. Westerheide, Richard I Morimoto*

*Corresponding author for this work

Research output: Contribution to journalShort survey

344 Citations (Scopus)

Abstract

The disruption of protein folding quality control results in the accumulation of non-native protein species that can form oligomers, aggregates, and inclusions indicative of neurodegenerative disease. Likewise for over 100 other human diseases of protein conformation, a common feature may be the formation of off-path way folding intermediates that are unstable, self-associate, and with time lead to a chronic imbalance in protein homeostasis with deleterious consequences on cellular function. This has led to a hypothesis that enhancement of components of the cellular quality control machinery, specifically the levels and activities of molecular chaperones, suppress aggregation and toxicity phenotypes to allow cellular function to be restored. This review addresses the regulation of molecular chaperones and components of protein homeostasis by heat shock transcription factor 1 (HSF1), the master stress-inducible regulator, and our current understanding of pharmacologically active small molecule regulators of the heat shock response as a therapeutic strategy for protein conformational diseases.

Original languageEnglish (US)
Pages (from-to)33097-33100
Number of pages4
JournalJournal of Biological Chemistry
Volume280
Issue number39
DOIs
StatePublished - Sep 30 2005

Fingerprint

Heat-Shock Response
Protein Conformation
Modulators
Conformations
Molecular Chaperones
Quality Control
Proteins
Homeostasis
Quality control
Neurodegenerative diseases
Protein Folding
Protein folding
Therapeutics
Neurodegenerative Diseases
Oligomers
Machinery
Toxicity
Phenotype
Agglomeration
Hot Temperature

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "The disruption of protein folding quality control results in the accumulation of non-native protein species that can form oligomers, aggregates, and inclusions indicative of neurodegenerative disease. Likewise for over 100 other human diseases of protein conformation, a common feature may be the formation of off-path way folding intermediates that are unstable, self-associate, and with time lead to a chronic imbalance in protein homeostasis with deleterious consequences on cellular function. This has led to a hypothesis that enhancement of components of the cellular quality control machinery, specifically the levels and activities of molecular chaperones, suppress aggregation and toxicity phenotypes to allow cellular function to be restored. This review addresses the regulation of molecular chaperones and components of protein homeostasis by heat shock transcription factor 1 (HSF1), the master stress-inducible regulator, and our current understanding of pharmacologically active small molecule regulators of the heat shock response as a therapeutic strategy for protein conformational diseases.",
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Heat shock response modulators as therapeutic tools for diseases of protein conformation. / Westerheide, Sandy D.; Morimoto, Richard I.

In: Journal of Biological Chemistry, Vol. 280, No. 39, 30.09.2005, p. 33097-33100.

Research output: Contribution to journalShort survey

TY - JOUR

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