Endoplasmic reticulum stress leads to accumulation of wild-type SOD1 aggregates associated with sporadic amyotrophic lateral sclerosis.

ABSTRACT: Abnormal modifications to mutant superoxide dismutase 1 (SOD1) are linked to familial amyotrophic lateral sclerosis (fALS). Misfolding of wild-type SOD1 (SOD1^WT) is also observed in postmortem tissue of a subset of sporadic ALS (sALS) cases, but cellular and molecular mechanisms generating abnormal SOD1^WT species are unknown. We analyzed aberrant human SOD1^WT species over the lifetime of transgenic mice and found the accumulation of disulfide-cross-linked high-molecular-weight SOD1^WT aggregates during aging. Subcellular fractionation of spinal cord tissue and protein overexpression in NSC-34 motoneuron-like cells revealed that endoplasmic reticulum (ER) localization favors oxidation and disulfide-dependent aggregation of SOD1^WT We esta

SUBMITTER: Medinas DB 

PROVIDER: S-EPMC6094144 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature