title: SOD1 aggregation in ALS mice shows simplistic test tube behavior.
abstract: A longstanding challenge in studies of neurodegenerative disease has been that the pathologic protein aggregates in live tissue are not amenable to structural and kinetic analysis by conventional methods. The situation is put in focus by the current progress in demarcating protein aggregation in vitro, exposing new mechanistic details that are now calling for quantitative in vivo comparison. In this study, we bridge this gap by presenting a direct comparison of the aggregation kinetics of the ALS-associated protein superoxide dismutase 1 (SOD1) in vitro and in transgenic mice. The results based on tissue sampling by quantitative antibody assays show that the SOD1 fibrillation kinetics in vitro mirror with remarkable accuracy the spinal cord aggregate buildup and disease progression in transgenic mice. This similarity between in vitro and in vivo data suggests that, despite the complexity of live tissue, SOD1 aggregation follows robust and simplistic rules, providing new mechanistic insights into the ALS pathology and organism-level manifestation of protein aggregation phenomena in general.
authors.affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories of Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden;
authors.forename: Lisa
authors.initials: L
authors.lastname: Lang
authors.affiliation: Department of Medical Biosciences, Umeå University, SE-90186 Umeå, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Zetterström
authors.affiliation: Department of Medical Biosciences, Umeå University, SE-90186 Umeå, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brännström
authors.affiliation: Department of Medical Biosciences, Umeå University, SE-90186 Umeå, Sweden.
authors.forename: Stefan L
authors.initials: SL
authors.lastname: Marklund
authors.affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories of Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden;
authors.forename: Jens
authors.initials: J
authors.lastname: Danielsson
authors.affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories of Natural Sciences, Stockholm University, S-106 91 Stockholm, Sweden; mikael.oliveberg@dbb.su.se.
authors.forename: Mikael
authors.initials: M
authors.lastname: Oliveberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000473:pathology*; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D007700:Kinetics; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D066329:Protein Aggregates; D058767:Protein Unfolding; D013116:Spinal Cord / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D016019:Survival Analysis
chemical_list: D001059:Apoproteins; D066329:Protein Aggregates; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: aggregation; aggregation kinetics; superoxide dismutase 1; transgenic mice