Small molecule activators of the heat shock response: chemical properties, molecular targets, and therapeutic promise.
All cells have developed various mechanisms to respond and adapt to a variety of environmental challenges, including stresses that damage cellular proteins. One such response, the heat shock response (HSR), leads to the transcriptional activation of a family of molecular chaperone proteins that promote proper folding or clearance of damaged proteins within the cytosol. In addition to its role in protection against acute insults, the HSR also regulates lifespan and protects against protein misfolding that is associated with degenerative diseases of aging. As a result, identifying pharmacological regulators of the HSR has become an active area of research in recent years. Here, we review progress made in identifying small molecule activators of the HSR, what cellular targets these compounds interact with to drive response activation, and how such molecules may ultimately be employed to delay or reverse protein misfolding events that contribute to a number of diseases.
Biochemistry and Molecular Biology Program, Departments of Biology and Chemistry, The College of Wooster, Wooster, Ohio 44691, USA. jwest@wooster.edu
James D
JD
West
Yanyu
Y
Wang
Kevin A
KA
Morano
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D017510:Protein Folding / Q000187:drug effects; D057165:Proteostasis Deficiencies / Q000188:drug therapy; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D054852:Small Molecule Libraries; D014157:Transcription Factors