Insights into amyloid-beta-induced mitochondrial dysfunction in Alzheimer disease

Free Radic Biol Med. 2007 Dec 15;43(12):1569-73. doi: 10.1016/j.freeradbiomed.2007.09.007. Epub 2007 Sep 21.

Abstract

Amyloid-beta has long been implicated in the pathogenesis of Alzheimer disease. The focus was initially on the extracellular fibrillar deposits of amyloid-beta but more recently has shifted to intracellular oligomeric forms of amyloid-beta. Unfortunately, the mechanism(s) by which either extracellular or intracellular amyloid-beta induces neuronal toxicity remains unclear. That said, a number of recent studies indicate that mitochondria might be an important target of amyloid-beta. Neurons rely heavily on mitochondria for energy and it is well established that mitochondrial dysfunction might be an important target of amyloid-beta. Mechanistically, amyloid-beta aggregates in mitochondria to impair function, leading to energy hypometabolism and elevated reactive oxygen species production. Additionally, amyloid-beta affects the balance of mitochondrial fission/fusion and mitochondrial transport, negatively impacting a host of cellular functions of neurons. Here, we review the role that amyloid-beta plays in mitochondrial structure and function of neurons and the importance of this in the pathogenesis of Alzheimer disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Free Radicals / metabolism
  • Humans
  • Mitochondria / metabolism*
  • Multiprotein Complexes
  • Neurons / metabolism

Substances

  • Amyloid beta-Peptides
  • Free Radicals
  • Multiprotein Complexes