Figure 5.

Proposed mechanisms for S-Nitrosylation and Denitrosylation. While NO-mediated protein S-nitrosylation is generally a non-enzymatic reaction, mediated by RNS and ROS species and NOS-mediated NO production, denitrosylation can be both enzymatic and non-enzymatic. The major denitrosylase systems in cells are the Thr/ThrR and glutathione GSH/GSNOR. Moreover, SOD can have denitrosylase functions. The transnitrosylation of a protein can be directly performed by an already S-nitrosylated protein in close proximity. During aging, a subset of proteins is S-nitrosylated, promoting cell signaling cascades that aim for neuroprotection. Upon increased levels of RNS, potentially at early stages of neurodegeneration, increased levels of S-nitrosylation modulate multiple cellular processes and trigger the adjustment of signaling cascades in highly nitrosative environments. Aberrant S-nitrosylation in neurodegenerative disorders exacerbates disease pathology, ultimately leading to neuronal damage. Created with BioRender.com.