title: Progress in the pathogenesis and genetics of Parkinson's disease.
abstract: Recent progresses in the pathogenesis of sporadic Parkinson's disease (PD) and genetics of familial PD are reviewed. There are common molecular events between sporadic and familial PD, particularly between sporadic PD and PARK1-linked PD due to alpha-synuclein (SNCA) mutations. In sporadic form, interaction of genetic predisposition and environmental factors is probably a primary event inducing mitochondrial dysfunction and oxidative damage resulting in oligomer and aggregate formations of alpha-synuclein. In PARK1-linked PD, mutant alpha-synuclein proteins initiate the disease process as they have increased tendency for self-aggregation. As highly phosphorylated aggregated proteins are deposited in nigral neurons in PD, dysfunctions of proteolytic systems, i.e. the ubiquitin-proteasome system and autophagy-lysosomal pathway, seem to be contributing to the final neurodegenerative process. Studies on the molecular mechanisms of nigral neuronal death in familial forms of PD will contribute further on the understanding of the pathogenesis of sporadic PD.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo, Tokyo 113, Japan. y_mizuno@med.juntendo.ac.jp
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kubo
authors.forename: Shigeto
authors.initials: S
authors.lastname: Sato
authors.forename: Kenya
authors.initials: K
authors.lastname: Nishioka
authors.forename: Taku
authors.initials: T
authors.lastname: Hatano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Machida
authors.forename: Hideki
authors.initials: H
authors.lastname: Mochizuki
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein