Therapeutics aspects of Protein Denitrosylation

Nitric oxide is a fundamental second messenger regulating cell physiology through a variety of different signaling mechanisms. The majority of NO bio- activity is exerted via binding to cysteine residues of proteins, a reaction called S-nitrosylation that affects protein function and stability. Among NO-mediated signaling, S-nitrosylation is emerging as a central mechanism in cellular homeostasis by controlling processes that are often deregulated in pathological conditions. For these reasons, it is a constantly growing interest in targeting S-nitrosylation for therapeutic purposes. To overcome the difficulties in manipulating S-nitrosylation without inter- fering with other NO-mediated signaling pathways, researchers moved their attention to the molecular systems assigned to remove NO from proteins (deni- trosylases). Here, we review the most recent therapeutic approaches targeting protein denitrosylation, focusing on the two main systems: GSNOR and thioredoxin.