title: Role of mitochondrial dysfunction in Parkinson's disease: Implications for treatment.
abstract: The role of mitochondrial dysfunction as a possible cause of parkinsonism became apparent in the mid-1980s with the discovery of a group of individuals with chronic parkinsonism who had been exposed to the chemical 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the subsequent elucidation of the mode of action of this toxin as a mitochondrial complex I inhibitor. Thereafter, a defect in mitochondrial complex I was supported by biochemical studies in patients with sporadic Parkinson's disease. Recently, striking genetic findings and biological studies have further substantiated that mitochondrial dysfunction is likely an important disease mechanism in a significant percentage, if not the majority, of patients with Parkinson's disease. These findings have defined novel biochemical pathways that can directly or indirectly affect mitochondrial function and/or integrity. Although various primary insults (genetic or environmental factors) are involved in the aetiology of Parkinson's disease, emerging evidence supports the notion that attempting to prevent or compensate for mitochondrial dysfunction could have therapeutic benefits for a majority of patients with Parkinson's disease.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA.
authors.forename: Chenere P
authors.initials: CP
authors.lastname: Ramsey
authors.forename: Benoit I
authors.initials: BI
authors.lastname: Giasson
mesh_terms: D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D009498:Neurotoxins; D010300:Parkinson Disease / Q000209:etiology* / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051844:alpha-Synuclein / Q000502:physiology
chemical_list: D009498:Neurotoxins; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases