Neurochemical Research

, Volume 29, Issue 3, pp 569–577 | Cite as

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

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.

Oxidative stress complex I deficiency Parkinson's disease reactive oxygen species dopaminergic neurons 

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Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  1. 1.Department of Medical BiochemistrySemmelweis UniversityHungary
  2. 2.Neurochemistry GroupHungarian Academy of SciencesBudapestHungary

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