title: Features of wild-type human SOD1 limit interactions with misfolded aggregates of mouse G86R Sod1.
abstract: Mutations in the gene encoding superoxide dismutase 1 (SOD1) account for about 20% of the cases of familial amyotrophic lateral sclerosis (fALS). It is well established that mutations in SOD1, associated with fALS, heighten the propensity of the protein to misfold and aggregate. Although aggregation appears to be a factor in the toxicity of mutant SOD1s, the precise nature of this toxicity has not been elucidated. A number of other studies have now firmly established that raising the levels of wild-type (WT) human SOD1 (hSOD1) proteins can in some manner augment the toxicity of mutant hSOD1 proteins. However, a recent study demonstrated that raising the levels of WT-hSOD1 did not affect disease in mice that harbor a mouse Sod1 gene (mSod1) encoding a well characterized fALS mutation (G86R). In the present study, we sought a potential explanation for the differing effects with WT-hSOD1 on the toxicity of mutant hSOD1 versus mutant mSod1. In the cell culture models used here, we observe poor interactions between WT-hSOD1 and misfolded G86R-mSod1, possibly explaining why over-expression of WT-hSOD1 does not synergize with mutant mSod1 to accelerate the course of the disease in mice.
authors.forename: David A
authors.initials: DA
authors.lastname: Qualls
authors.forename: Mercedes
authors.initials: M
authors.lastname: Prudencio
authors.forename: Brittany L T
authors.initials: BL
authors.lastname: Roberts
authors.forename: Keith
authors.initials: K
authors.lastname: Crosby
authors.forename: Hilda
authors.initials: H
authors.lastname: Brown
authors.affiliation: From the Department of Neuroscience, Center for Translational Research in Neurodegenerative Disease, SantaFe HealthCare Alzheimer's Disease Research Center, McKnight Brain Institute, University of Florida, Box 100159, 1275 Center Drive, Room J491, Gainesville, FL 32610, USA. drb1@ufl.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Borchelt
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D017510:Protein Folding; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014162:Transfection
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1