title: Intracellular seeded aggregation of mutant Cu,Zn-superoxide dismutase associated with amyotrophic lateral sclerosis.
abstract: Once a protein adopts the fibrillar aggregate conformation, a seeding reaction becomes operative in which pre-formed fibrils function as seeds for soluble protein molecules to be fibrillized. Such a seeding reaction accelerates the protein fibrillation in vitro; however, more investigation is required to test the seeded fibrillation inside cells. Here, we show that in vitro Cu,Zn-superoxide dismutase (SOD1) fibrils are transduced into cells and function as seeds to trigger the aggregation of endogenously expressed SOD1. Seeded aggregation of mutant SOD1 will thus play roles in a molecular pathomechanism of SOD1-linked amyotrophic lateral sclerosis.
authors.affiliation: Laboratory for Mechanistic Chemistry of Biomolecules, Department of Chemistry, Keio University, Yokohama, Kanagawa 223-8522, Japan. furukawa@chem.keio.ac.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Kumi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Shoji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D017510:Protein Folding; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: D000682:Amyloid; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: ALS; Amyloid; Neurodegenerative disease; Protein aggregation; SOD1