Superoxide dismutase 1 encoding mutations linked to ALS adopts a spectrum of misfolded states.

ABSTRACT:

Background

Mutations in superoxide dismutase 1 (SOD1), which are one cause of familial amyotrophic lateral sclerosis (fALS), induce misfolding and aggregation of the protein. Misfolding can be detected by the binding of antibodies raised against peptide epitopes that are normally buried in the native conformation, shifts in solubility in non-ionic detergents, and the formation of macromolecular inclusions. In the present study, we investigate the relationship between detergent-insoluble and sedimentable forms of mutant SOD1, forms of mutant SOD1 with aberrantly accessible epitopes, and mutant protein in inclusions with the goal of defining the spectrum of misfolded states that mutant SOD1 can adopt.

Results

Using combined approaches in cultured cell models, we demonstrate th

SUBMITTER: Prudencio M 

PROVIDER: S-EPMC3248846 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature