Amyloid beta peptide induces cytochrome C release from isolated mitochondria

Neuroreport. 2002 Oct 28;13(15):1989-93. doi: 10.1097/00001756-200210280-00032.

Abstract

Amyloid beta peptide (Abeta) is a neurotoxic metabolic product of the amyloid precursor protein (APP). Abeta is strongly implicated in the pathology of Alzheimer's disease (AD) and can be formed intracellularly. In this study, we show that the addition of Abeta to isolated mouse brain mitochondria can directly induce cytochrome c (Cyt c) release and mitochondrial swelling, which were partially inhibited by cyclosporin A (CsA). These results suggest that the Abetaaccumulated intracellularly by APP processing might exert neurotoxicity by interacting with mitochondria and inducing mitochondrial swelling and release of Cyt c, which activates caspase-3 and finally can lead to apoptosis in neuronal cells and to neurodegeneration in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain / drug effects
  • Brain / enzymology*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Caspase 3
  • Caspases / drug effects
  • Caspases / metabolism
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / physiology
  • Cells, Cultured
  • Cyclosporine / pharmacology
  • Cytochrome c Group / drug effects
  • Cytochrome c Group / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / enzymology*
  • Neurons / drug effects
  • Neurons / enzymology*
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / metabolism*
  • Peptide Fragments / toxicity

Substances

  • Amyloid beta-Peptides
  • Cytochrome c Group
  • Enzyme Inhibitors
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Cyclosporine
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases