Nitric oxide-mediated S-nitrosylation pathway (SNO pathway)

Nitric oxide-mediated S-nitrosylation is a fundamental post-translational modification where a nitric oxide (NO) moiety is covalently attached to a protein cysteine thiol to form an S-nitrosothiol (SNO) (Hess et al., 2005, Nature Reviews Molecular Cell Biology). This pathway acts as a ubiquitous signaling mechanism, analogous to phosphorylation, regulating a wide array of cellular processes including vasodilation, metabolic homeostasis, and apoptosis (Stamler et al., 2001, Neuron). In various disease states, dysregulated S-nitrosylation—either through excessive nitrosative stress or deficient NO bioavailability—is linked to cardiovascular disorders, neurodegeneration (e.g., Parkinson's), and respiratory diseases like asthma and cystic fibrosis (Foster et al., 2009, Trends in Molecular Medicine). Pharmacological intervention typically involves NO donors to increase S-nitrosylation or inhibitors of S-nitrosoglutathione reductase (GSNOR) to prevent the breakdown of endogenous S-nitrosothiols (Green et al., 2012, Progress in Respiratory Research). While therapeutically promising, the primary challenge in targeting this pathway is the lack of molecular specificity, as NO can modify numerous proteins simultaneously, potentially leading to systemic side effects such as hypotension.

Other names

Protein S-nitrosylationS-nitrosationS-nitrosothiol signalingNitrosative signalingNO-mediated S-nitrosation

Nitric oxide donation to increase S-nitrosothiol formation; Inhibition of S-nitrosoglutathione reductase (GSNOR) to prevent the catabolism of S-nitrosoglutathione (GSNO); Direct chemical S-nitrosylation of protein cysteine thiols.