Complex I deficiency in Parkinson's disease frontal cortex.
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.
Parker
W Davis
WD
Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. dp8m@virginia.edu
Parks
Janice K
JK
Swerdlow
Russell H
RH
D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay / Q000379:methods / Q000592:standards; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001928:Brain Diseases, Metabolic / Q000378:metabolism* / Q000503:physiopathology; D042967:Electron Transport Complex I / Q000172:deficiency*; D004734:Energy Metabolism / Q000502:physiology; D005625:Frontal Lobe / Q000378:metabolism* / Q000503:physiopathology; D006651:Histocytochemistry / Q000379:methods / Q000592:standards; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D011237:Predictive Value of Tests; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D051844:alpha-Synuclein; D042967:Electron Transport Complex I