To fold or not to fold: modulation and consequences of Hsp90 inhibition.
BACKGROUND
The 90-kDa heat-shock proteins (Hsp90) have rapidly evolved into promising therapeutic targets for the treatment of several diseases, including cancer and neurodegenerative diseases. Hsp90 is a molecular chaperone that aids in the conformational maturation of nascent polypeptides, as well as the rematuration of denatured proteins.


CONCLUSIONS
Many of the Hsp90-dependent client proteins are associated with cellular growth and survival and, consequently, inhibition of Hsp90 represents a promising approach for the treatment of cancer. Conversely, stimulation of heat-shock protein levels has potential therapeutic applications for the treatment of neurodegenerative diseases that result from misfolded and aggregated proteins.


CONCLUSIONS
Hsp90 modulation exhibits the potential to treat unrelated disease states, from cancer to neurodegenerative diseases, and, thus, to fold or not to fold, becomes a question of great value.
Peterson
Laura B
LB
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KA 66045-7563, USA. bblagg@ku.edu
Blagg
Brian S J
BS
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009422:Nervous System Diseases / Q000188:drug therapy; D017510:Protein Folding; D054852:Small Molecule Libraries / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018841:HSP90 Heat-Shock Proteins; D054852:Small Molecule Libraries; D016875:tau Proteins