title: Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimers disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Abeta) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Abeta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Abeta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Abeta amino acids 26-42. Interestingly, intracellular Ab binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Abeta in the development of ALS by interacting with the SOD1 G93A mutant.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Yoon
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Goo Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Cho
authors.forename: Jung Ha
authors.initials: JH
authors.lastname: Choi
authors.forename: Hye Yoon
authors.initials: HY
authors.lastname: Park
authors.forename: Ja Young
authors.initials: JY
authors.lastname: Jang
authors.forename: Hyang Shuk
authors.initials: HS
authors.lastname: Rhim
authors.forename: Seong Man
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology*; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D016229:Amyloid beta-Peptides; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1