title: Oxidized glutathione stimulated the amyloid formation of alpha-synuclein.
abstract: alpha-Synuclein is the major filamentous constituent of Lewy bodies found in Parkinson's disease (PD). The amyloid formation of alpha-synuclein was significantly facilitated by oxidized glutathione (GSSG) as the lag period of the aggregation kinetics was shortened by 2.5-fold from its absence. Reduced glutathione (GSH), on the other hand, did not influence the lag phase although it increased the final amyloid formation. The GSSG stimulation was specific for not only alpha-synuclein but also its intactness. The preferred GSSG interaction of alpha-synuclein to GSH was also demonstrated with dissociation constants of 0.53 and 43.5 mM, respectively. It is suggested that the oxidative stress favoring the GSSG generation from GSH could result in the augmented amyloid formation of alpha-synuclein, which ought to be related to the pathogenesis of PD.
authors.affiliation: Department of Biochemistry, College of Medicine, Inha University, 253 Yonghyun-Dong, Nam-Ku, Inchon 402-751, South Korea. srpaik@inha.ac.kr
authors.forename: Seung R
authors.initials: SR
authors.lastname: Paik
authors.forename: Daekyun
authors.initials: D
authors.lastname: Lee
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Cho
authors.forename: Eui-Nam
authors.initials: EN
authors.lastname: Lee
authors.forename: Chung-Soon
authors.initials: CS
authors.lastname: Chang
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism*; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D000682:Amyloid; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D051843:Synucleins; D051844:alpha-Synuclein; D005978:Glutathione; D019803:Glutathione Disulfide