Mechanism of oxidative stress in neurodegeneration

Oxid Med Cell Longev. 2012;2012:428010. doi: 10.1155/2012/428010. Epub 2012 May 16.

Abstract

Biological tissues require oxygen to meet their energetic demands. However, the consumption of oxygen also results in the generation of free radicals that may have damaging effects on cells. The brain is particularly vulnerable to the effects of reactive oxygen species due to its high demand for oxygen, and its abundance of highly peroxidisable substrates. Oxidative stress is caused by an imbalance in the redox state of the cell, either by overproduction of reactive oxygen species, or by dysfunction of the antioxidant systems. Oxidative stress has been detected in a range of neurodegenerative disease, and emerging evidence from in vitro and in vivo disease models suggests that oxidative stress may play a role in disease pathogenesis. However, the promise of antioxidants as novel therapies for neurodegenerative diseases has not been borne out in clinical studies. In this review, we critically assess the hypothesis that oxidative stress is a crucial player in common neurodegenerative disease and discuss the source of free radicals in such diseases. Furthermore, we examine the issues surrounding the failure to translate this hypothesis into an effective clinical treatment.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / therapeutic use
  • Brain / enzymology
  • Brain / metabolism
  • Mitochondria / metabolism
  • Models, Theoretical
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Oxidative Stress*
  • Oxidoreductases / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Oxidoreductases