Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis

Neurology. 2006 Jan 24;66(2 Suppl 1):S74-8. doi: 10.1212/01.wnl.0000192103.24796.42.

Abstract

Recent findings indicate that soluble amyloid oligomers may represent the primary pathologic species in degenerative diseases. These amyloid oligomers share common structural features and the ability to permeabilize membranes, suggesting that they also share a common primary mechanism of pathogenesis. Membrane permeabilization by amyloid oligomers may initiate a common group of downstream pathologic processes, including intracellular calcium dyshomeostasis, production of reactive oxygen species, altered signaling pathways, and mitochondrial dysfunction that represent key effectors of cellular dysfunction and cell death in amyloid-associated degenerative disease, such as sporadic inclusion-body myositis.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Amyloid / chemistry
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / immunology
  • Amyloidosis / etiology
  • Amyloidosis / metabolism
  • Animals
  • Antibody Specificity
  • Biopolymers
  • Calcium / metabolism
  • Cell Membrane Permeability
  • Dementia / etiology
  • Dementia / metabolism
  • Drug Design
  • Humans
  • Huntington Disease / etiology
  • Huntington Disease / metabolism
  • Inclusion Bodies / chemistry
  • Mice
  • Mice, Transgenic
  • Mitochondria / physiology
  • Myositis, Inclusion Body / etiology
  • Myositis, Inclusion Body / metabolism
  • Parkinson Disease / etiology
  • Parkinson Disease / metabolism
  • Protein Folding
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Solubility
  • Structure-Activity Relationship

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Biopolymers
  • Reactive Oxygen Species
  • Calcium