title: [Cellular pathophysiology of Parkinson's disease].
abstract: To explore pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy, we developed cellular model for synucleinopathy. In this experimental model, alpha-synuclein was overexpressed in SH-SY5Y cells, which were then exposed to mitochondrial toxins. The data thus obtained suggested the followings. (1) By the treatment with rotenone, wild type alpha-synuclein overexpressing cells demonstrated intracellular aggregations, which shared a number of features with Lewy bodies. (2) The aggregate formation of alpha-synuclein may be cytoprotective. (3) The catechol-derived quinones are candidate molecules to facilitate the oligomer formation of a-synuclein. (4) The cells overexpressing S129A mutant showed few aggregations. It is suggested that phosphorylation at serine 129 is essential for aggregate formation. (5) In wild-type alpha-synuclein cells treated with rotenone, unfolded protein response (UPR) markers were induced prior to the induction of mitochondrial disruption and caspase-3 activation. (6) On the other hand, the S129A mutant failed to activate these UPRs. Thus it seems plausible that alpha-synuclein toxicity is dependent on the phosphorylation at S129.
authors.affiliation: Division of Neurology, Department of Neuroscience & Sensory Organs, Tohoku University, Graduate School of Medicine.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Naoto
authors.initials: N
authors.lastname: Sugeno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Michiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Akio
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D000371:Agglutination; D053148:Caspase 3 / Q000378:metabolism; D004721:Endoplasmic Reticulum; D006801:Humans; D016631:Lewy Bodies; D009154:Mutation; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology*; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D011809:Quinones; D012402:Rotenone; D051844:alpha-Synuclein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011809:Quinones; D051844:alpha-Synuclein; D012402:Rotenone; D053148:Caspase 3