title: Protein aggregation in the pathogenesis of familial and sporadic Parkinson's disease.
abstract: Parkinson's disease (PD) is a slowly progressive, age-related, neurodegenerative disorder. The cause and mechanism of neuronal death have been elusive. However, recent genetic, postmortem and experimental evidence show that protein accumulation and aggregation are prominent occurrences in both sporadic and familial PD. The relevance of these events to other cellular and biochemical changes, and to the neurodegenerative process, is being unraveled. It is increasingly evident that one or a combination of defects, including mutations, oxidative stress, mitochondrial impairment and dysfunction of the ubiquitin-proteasome system, lead to an excess production and aggregation of abnormal proteins in PD. In this respect, altered protein handling appears to be a central factor in the pathogenic process occurring in the various hereditary and sporadic forms of PD. This suggests that manipulation of proteolytic systems is a rational approach in the development of neuroprotective therapies that could modify the pathological course of PD.
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, Annenberg 14-73, One Gustave L. Levy Place, New York, NY 10029, USA. kevin.mcnaught@mssm.edu
authors.forename: Kevin St P
authors.initials: KS
authors.lastname: McNaught
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
mesh_terms: D000818:Animals; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex