To fold or not to fold: modulation and consequences of Hsp90 inhibition

Abstract

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. Discussion: 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. Conclusion: 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.