Free radicals and mitochondrial dysfunction in Parkinson's disease.
The precise relationship of the complex I deficiency in PD to the dopaminergic cell death and aetiology of this disorder is as yet unknown. However, evidence is accruing that this mitochondrial defect may play a central role in the cascade of events that terminates in nigral neuronal loss. Further work needs to be carried out to determine the molecular mechanisms that underlie the complex I deficiency as these may provide important indicators to the ultimate cause of PD. This may involve a genetic abnormality of complex I that may convey a susceptibility to developing PD. Alternatively, exogenous or endogenous toxic agents may target nigral complex I along pathways similar to those recognized for MPTP. A combination of a genetic predisposition in addition to an environmental precipitant has gained substantial support as an explanation for the cause of PD.
Schapira
A H
AH
Department of Neuroscience, Royal Free Hospital School of Medicine, London, U.K.
Hartley
A
A
Cleeter
M W
MW
Cooper
J M
JM
D016923:Cell Death; D005609:Free Radicals; D006801:Humans; D007501:Iron / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism
D005609:Free Radicals; D007501:Iron