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

Future Med Chem. 2009 May;1(2):267-83. doi: 10.4155/fmc.09.17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / physiology
  • Humans
  • Neoplasms / drug therapy
  • Nervous System Diseases / drug therapy
  • Protein Folding
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / therapeutic use
  • Small Molecule Libraries / toxicity
  • tau Proteins / chemistry
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • HSP90 Heat-Shock Proteins
  • Small Molecule Libraries
  • tau Proteins