Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson's disease.
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, alpha-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.
Tretter
Laszlo
L
Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
Sipos
Ildiko
I
Adam-Vizi
Vera
V
D042967:Electron Transport Complex I / Q000172:deficiency*; D004734:Energy Metabolism; D006801:Humans; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000201:enzymology / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I