Protein folding, nucleation phenomena and delayed neurodegeneration in Alzheimer's disease

Rev Neurosci. 1996 Jan-Mar;7(1):21-8. doi: 10.1515/revneuro.1996.7.1.21.

Abstract

This hypothesis attempts to explain how Alzheimer's disease can be both sporadic and autosomal dominant with catastrophic neurodegeneration occurring after decades of normal function. The production of A beta peptide, the subunit of amyloid plaques, from the ubiquitous amyloid precursor protein is discussed. Conformational changes are argued to be crucial to the formation of these amyloid plaques and to their neurotoxicity. Parallels are drawn with prion disease where similarly a normal cellular protein becomes pathogenic once a conformational change is induced. Post-mitotic neurons in the brain are susceptible to this destructive process which is initiated by nucleation phenomena and is then self propagating. An understanding of the conformational changes involved in plaque formation may open new therapeutic avenues in Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Humans
  • Nerve Degeneration / physiology*
  • Neurofibrillary Tangles / metabolism*
  • Neurofibrillary Tangles / pathology
  • Protein Folding*