Heat shock protein 90: translation from cancer to Alzheimer's disease treatment?

BMC Neurosci. 2008 Dec 3;9 Suppl 2(Suppl 2):S7. doi: 10.1186/1471-2202-9-S2-S7.

Abstract

Both malignant transformation and neurodegeneration, as it occurs in Alzheimer's disease, are complex and lengthy multistep processes characterized by abnormal expression, post-translational modification, and processing of certain proteins. To maintain and allow the accumulation of these dysregulated processes, and to facilitate the step-wise evolution of the disease phenotype, cells must co-opt a compensatory regulatory mechanism. In cancer, this role has been attributed to heat shock protein 90 (Hsp90), a molecular chaperone that maintains the functional conformation of multiple proteins involved in cell-specific oncogenic processes. In this sense, at the phenotypic level, Hsp90 appears to serve as a biochemical buffer for the numerous cancer-specific lesions that are characteristic of diverse tumors. The current review proposes a similar role for Hsp90 in neurodegeneration. It will present experimentally demonstrated, but also hypothetical, roles that suggest Hsp90 can act as a regulator of pathogenic changes that lead to the neurodegenerative phenotype in Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / physiology
  • Humans
  • Models, Biological
  • Molecular Chaperones / antagonists & inhibitors
  • Molecular Chaperones / metabolism
  • Molecular Chaperones / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / physiopathology
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology

Substances

  • Amyloid beta-Peptides
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones