The molecular pathogenesis of superoxide dismutase 1-linked ALS is promoted by low oxygen tension.

ABSTRACT: Mutations in superoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS). Disease pathogenesis is linked to destabilization, disorder and aggregation of the SOD1 protein. However, the non-genetic factors that promote disorder and the subsequent aggregation of SOD1 have not been studied. Mainly located to the reducing cytosol, mature SOD1 contains an oxidized disulfide bond that is important for its stability. Since O₂ is required for formation of the bond, we reasoned that low O₂ tension might be a risk factor for the pathological changes associated with ALS development. By combining biochemical approaches in an extensive range of genetically distinct patient-derived cell lines, we show that the disulfide bond is an Achilles heel of the SOD1 protein. Cultu

SUBMITTER: Keskin I 

PROVIDER: S-EPMC6570705 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature