Initiation of Neuronal Damage by Complex I Deficiency and Oxidative Stress in Parkinson's Disease

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137 Citations (Scopus)

Abstract

Oxidative stress and partial deficiencies of mitochondrial complex I appear to be key factors in the pathogenesis of Parkinson's disease. They are interconnected; complex I inhibition results in an enhanced production of reactive oxygen species (ROS), which in turn will inhibit complex I. Partial inhibition of complex I in nerve terminals is sufficient for in situ mitochondria to generate more ROS. H2O2 plays a major role in inhibiting complex I as well as a key metabolic enzyme, α-ketoglutarate dehydrogenase. The vicious cycle resulting from partial inhibition of complex I and/or an inherently higher ROS production in dopaminergic neurons leads over time to excessive oxidative stress and ATP deficit that eventually will result in cell death in the nigro-striatal pathway.

Original languageEnglish
Pages (from-to)569-577
Number of pages9
JournalNeurochemical research
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 1 2004

Keywords

  • Complex I deficiency
  • Dopaminergic neurons
  • Oxidative stress
  • Parkinson's disease
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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