TY - JOUR
T1 - Heat shock response modulators as therapeutic tools for diseases of protein conformation
AU - Westerheide, Sandy D.
AU - Morimoto, Richard I.
PY - 2005/9/30
Y1 - 2005/9/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=25844466597&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25844466597&partnerID=8YFLogxK
U2 - 10.1074/jbc.R500010200
DO - 10.1074/jbc.R500010200
M3 - Short survey
C2 - 16076838
AN - SCOPUS:25844466597
SN - 0021-9258
VL - 280
SP - 33097
EP - 33100
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 39
ER -