Familial Alzheimer's disease: oxidative stress, beta-amyloid, presenilins, and cell death

Gen Pharmacol. 1998 Nov;31(5):675-81. doi: 10.1016/s0306-3623(98)00189-x.

Abstract

1. The basic etiology of Alzheimer's disease remains unknown, although four genes have so far been involved: beta-amyloid precursor protein, presenilin-1, presenilin-2 and apolipoprotein E genes. 2. The largest familial Alzheimer's disease (FAD) kindred so far reported belong to a point mutation in codon 280 that results in a glutamic acid-to-alanine substitution in presenilin-1 characterized in Antioquia, Colombia. 3. A hypothetical unified molecular mechanism model of cell death in FAD mediated by presenilin-1, beta-amyloid, and oxidative stress is proposed as an attempt to explain the mechanisms of neuronal loss in this neurodegenerative disorder.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cell Death
  • Humans
  • Membrane Proteins / metabolism*
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress*
  • Presenilin-1
  • Presenilin-2

Substances

  • Amyloid beta-Peptides
  • Membrane Proteins
  • Neuroprotective Agents
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2