Stress-inducible responses and heat shock proteins: new pharmacologic targets for cytoprotection.
Molecular chaperones protect proteins against environmental and physiologic stress and from the deleterious consequences of an imbalance in protein homeostasis. Many of these stresses, if prolonged, result in defective development and pathologies associated with a diverse array of diseases due to tissue injury and repair including stroke, myocardial reperfusion damage, ischemia, cancer, amyloidosis, and other neurodegenerative diseases. We discuss the molecular nature of the stress signals, the mechanisms that underlie activation of the heat shock response, the role of heat shock proteins as cytoprotective molecules, and strategies for pharmacologically active molecules as regulators of the heat shock response.
Morimoto
R I
RI
Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA. r-morimoto@nwu.edu
Santoro
M G
MG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016227:Benzoquinones; D002470:Cell Survival / Q000187:drug effects*; D015195:Drug Design; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D018869:Heat-Shock Response; D006801:Humans; D019811:Hydroxylamine / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D018384:Oxidative Stress / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D006360:Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; D019811:Hydroxylamine; C020754:herbimycin