title: Parkinson's disease, proteins, and prions: milestones.
abstract: Parkinson's disease (PD) is characterized by protein accumulation in the form of Lewy bodies and neurites. It is thus reasonable to consider that alterations in protein handling in the form of increased production, impaired clearance, or both might be central to the etiopathogenesis of the disease. Increasing genetic, laboratory and pathologic evidence has accumulated over the past 25 years supporting this hypothesis. A vicious cycle could develop in which increased protein accumulation from any cause could lead to interference with lysosomal and proteasomal clearance mechanisms causing further protein accumulation. Eventually, protein accumulation could overwhelm the cell's defenses and lead to the formation of toxic oligomers and amyloid-based inclusions such as Lewy bodies, disruption of critical cell processes, and ultimately neurodegeneration. More recent findings of Lewy pathology in implanted embryonic dopamine neurons in PD patients raises the intriguing possibility that PD might be a prion disorder. These concepts suggests new targets and novel candidate therapies that might be neuroprotective for PD.
authors.affiliation: Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA. cwolanow@movementdisorders.org
authors.forename: C Warren
authors.initials: CW
authors.lastname: Olanow
authors.forename: K
authors.initials: K
authors.lastname: McNaught
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000266:history / Q000378:metabolism* / Q000628:therapy; D017096:Prion Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D011328:Prions; D025801:Ubiquitin