title: Evidence for mitochondrial dysfunction in Parkinson's disease--a critical appraisal.
abstract: There is now considerable evidence to support a defect of the mitochondrial respiratory chain, and complex I in particular, in Parkinson's Disease (PD). However, the site specificity of the defect within the chain, its anatomical selectivity within the brain, and its presence in other tissues still remain controversial. Much of the present confusion surrounding the mitochondrial defect can be dispelled by careful analysis of the available data. The molecular basis of the deficiency and its relevance to the pathogenesis of PD remain unknown. Nevertheless, the complex I deficiency in PD provides a direct biochemical link between the idiopathic disease and the MPTP toxin model. The relationship between the mitochondrial defect and other abnormalities within the PD substantia nigra suggests that a self amplifying cycle of events might be precipitated either by a genetic or environmentally induced abnormality of mitochondrial function or free radical metabolism. Alternatively, a biochemical event separate from these might precipitate a cascade which terminates in complex I dysfunction and free radical formation. An understanding of the molecular basis of the complex I defect in PD and its relationship to other biochemical changes will provide important insight into the potential chain of events that lead to dopaminergic cell death in PD.
authors.affiliation: Department of Neurosciences, Royal Free Hospital School of Medicine, London, U.K.
authors.forename: A H
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004272:DNA, Mitochondrial / Q000096:biosynthesis; D004579:Electron Transport / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000473:pathology / Q000502:physiology*; D008931:Mitochondria, Muscle / Q000473:pathology / Q000502:physiology; D017237:Mitochondrial Encephalomyopathies / Q000473:pathology / Q000503:physiopathology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D013378:Substantia Nigra / Q000473:pathology / Q000503:physiopathology
chemical_list: D004272:DNA, Mitochondrial; D016660:NAD(P)H Dehydrogenase (Quinone)