S-nitrosothiol signaling pathway (SNO signaling)

The S-nitrosothiol signaling pathway is a major mechanism for nitric oxide (NO) bioactivity, primarily mediated through the S-nitrosylation of cysteine residues on target proteins. This post-translational modification acts as a molecular switch, altering protein function, protein-protein interactions, and cellular localization across diverse physiological systems. The pathway is tightly regulated by enzymes such as S-nitrosoglutathione reductase (GSNOR) and thioredoxin, which facilitate the removal of the nitroso group in a process called denitrosylation. Imbalances in S-nitrosothiol levels are linked to numerous diseases, including respiratory conditions like asthma and cystic fibrosis, as well as cardiovascular and neurodegenerative disorders. In the lungs, S-nitrosothiols like S-nitrosoglutathione (GSNO) act as potent endogenous bronchodilators, and their depletion is associated with airway inflammation and hyperresponsiveness. Therapeutic interventions targeting this pathway include GSNOR inhibitors, which aim to increase the levels of protective S-nitrosothiols by preventing their degradation. Additionally, S-nitrosothiol donors are being explored as a means to restore NO-like bioactivity in conditions characterized by NO deficiency or resistance.

Other names

S-nitrosylation pathwaySNO-mediated signalingNitrosative stress signalingS-nitrosothiol metabolism

Modulation of S-nitrosothiol levels through inhibition of denitrosylating enzymes (e.g., GSNOR) or direct delivery of S-nitrosothiol donors.