S-glutathionylation and endoplasmic reticulum stress in Parkinson's disease

Oxidative stress and endoplasmic reticulum (ER) stress are core contributing factors to neurodegeneration in Parkinson's disease (PD). Protein cysteine residues are sensitive to changes in cellular redox conditions functioning as stress sensors. S-glutathionylation is a specific post-translational modification of protein cysteine residues whereby glutathione may be reversibly bound to these amino acids protecting them from irreversible oxidation. We recently described a role for S-glutathionylation, mediated by Glutathione S-Transferase pi (GSTP), in the modulation of the Nrf2-Keap1 pathway underscoring its relevance in the homeostatic redox control. Herein we evaluated the expression levels of ER stress markers in human PD brains and C57BL/6 wt vs GSTP ko mice in a neurotoxin-induced PD model. The potential rescuing effect of TUDCA, a chemical chaperone that enhances ER adaptive capacity, was assessed. S-glutathionylation of relevant ER stress markers is also discussed. Our results demonstrate the involvement of ER stress in PD providing new insights into the role of GSTP in the modulation of ER stress through S-glutathionylation.