Preventing beta-amyloid fibrillization and deposition: beta-sheet breakers and pathological chaperone inhibitors

BMC Neurosci. 2008 Dec 3;9 Suppl 2(Suppl 2):S5. doi: 10.1186/1471-2202-9-S2-S5.

Abstract

Central to the pathogenesis of Alzheimer's disease (AD) is the conversion of normal, soluble beta-amyloid (sAbeta) to oligomeric, fibrillar Abeta. This process of conformational conversion can be influenced by interactions with other proteins that can stabilize the disease-associated state; these proteins have been termed 'pathological chaperones'. In a number of AD models, intervention that block soluble Abeta aggregation, including beta-sheet breakers, and compounds that block interactions with pathological chaperones, have been shown to be highly effective. When combined with early pathology detection, these therapeutic strategies hold great promise as effective and relatively toxicity free methods of preventing AD related pathology.

Publication types

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

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Humans
  • Molecular Chaperones / antagonists & inhibitors
  • Molecular Chaperones / metabolism
  • Neurofibrils / drug effects*
  • Neurofibrils / pathology
  • Plaque, Amyloid / drug effects
  • Plaque, Amyloid / pathology
  • Protein Structure, Secondary

Substances

  • Amyloid beta-Peptides
  • Molecular Chaperones