Potential effect of S-nitrosylated protein disulfide isomerase on mutant SOD1 aggregation and neuronal cell death in amyotrophic lateral sclerosis.

ABSTRACT: Aggregation of misfolded protein and resultant intracellular inclusion body formation are common hallmarks of mutant superoxide dismutase (mSOD1)-linked familial amyotrophic lateral sclerosis (FALS) and have been associated with the selective neuronal death. Protein disulfide isomerase (PDI) represents a family of enzymatic chaperones that can fold nascent and aberrant proteins in the endoplasmic reticulum (ER) lumen. Recently, our group found that S-nitrosylated PDI could contribute to protein misfolding and subsequent neuronal cell death. However, the exact role of PDI in the pathogenesis of ALS remains unclear. In this study, we propose that PDI attenuates aggregation of mutant/misfolded SOD1 and resultant neurotoxicity associated with ER stress. ER stress resulting in PDI dysfunction t

SUBMITTER: Jeon GS 

PROVIDER: S-EPMC5973792 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature