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.

• Authors: Laura B Peterson, Brian S J Blagg
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 1 Issue 2 Pg. 267-83 (May 2009) ISSN: 1756-8927 [Electronic] England
• PMID: 20161407 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

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

Topics

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