The Role of Protein S-Nitrosylation in Protein Misfolding-Associated Diseases

Abnormal and excessive nitrosative stress contributes to neurodegenerative disease associated with the production of pathological levels of misfolded proteins. The accumulated findings strongly suggest that excessive NO production can induce and deepen these pathological processes, particularly by the S-nitrosylation of target proteins. Therefore, the relationship between S-nitrosylated proteins and the accumulation of misfolded proteins was reviewed. We particularly focused on the S-nitrosylation of E3-ubiquitin-protein ligase, parkin, and endoplasmic reticulum chaperone, PDI, which contribute to the accumulation of misfolded proteins. In addition to the target proteins being S-nitrosylated, NOS, which produces NO, and GSNOR, which inhibits S-nitrosylation, were also suggested as potential therapeutic targets for protein misfolding-associated diseases.

Automated summary

Excessive nitrosative stress contributes to neurodegenerative diseases by producing misfolded proteins. The relationship between S-nitrosylated proteins and the accumulation of misfolded proteins was reviewed, with a focus on parkin and PDI. Therapeutic targets for protein misfolding-associated diseases include NOS and GSNOR, in addition to S-nitrosylated target proteins.