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

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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.

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Tretter, L., Sipos, I. & Adam-Vizi, V. Initiation of Neuronal Damage by Complex I Deficiency and Oxidative Stress in Parkinson's Disease. Neurochem Res 29, 569–577 (2004). https://doi.org/10.1023/B:NERE.0000014827.94562.4b

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