Idiopathic Parkinson's disease may have a low-level familial association but does not follow mendelian patterns of inheritance. Since inheritance of some components of the electron transport chain is nonmendelian and since inhibition of the electron transport chain with the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine models Parkinson's disease in humans and animals, we evaluated catalytic activities of the electron transport chain in platelet mitochondria purified from patients with idiopathic Parkinson's disease. All 10 patients studied had significant reductions of complex I (NADH:ubiquinone oxidoreductase) activity. Succinate:cytochrome c oxidoreductase activity was less strikingly reduced. We hypothesize that the complex I abnormality may have an etiological role in the pathogenesis of Parkinson's disease and that this defect may be derived via the mitochondrial genome.
We assayed cytochrome oxidase and other electron transport chain activities in platelet mitochondria isolated from patients with Alzheimer's disease (AD). Five of 6 patients had striking reductions of platelet cytochrome oxidase activity (patient mean, 83.72 +/- 82.99 nmol/min/mg; control mean, 167.14 +/- 36.21 nmol/min/mg; n = 8). Other electron transport chain catalytic activities were not significantly different than control values. AD may be a systemic illness, a primary defect in cytochrome oxidase may be pathogenically important in its production, and the mitochondrial genes encoding cytochrome oxidase subunits may be important in producing the defect.
A study of complex I (NADH:ubiquinone oxidoreductase) activity in Parkinson's disease (PD) brain has identified loss of activity only in substantia nigra although loss of activity of this enzyme has been identified in a number of non-brain tissues. We investigated this paradox by studying complex I and other complexes of the mitochondrial electron transport chain in frontal cortex from PD and aged control brain using a variety of assay conditions and tissue preparations. We found increasingly significant losses of complex I activity in PD frontal cortex as increasingly pure mitochondria were studied. Complexes II, III, and IV were comparable in PD and controls. Inclusion of bovine serum albumin in the assay increased enzyme activity but lessened discrimination between PD and controls. Complex I deficiency in PD brain is not confined to substantia nigra. Methodological issues are critical in demonstrating this loss of activity.
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