Signaling by hydrogen sulfide (H2S) and polysulfides (H2Sn) in the central nervous system

Hydrogen sulfide (H2S) is a signaling molecule used to modify neuronal transmission, regulate vascular tone, protect tissues from oxidative stress, sense oxygen, and generate ATP. Hydrogen polysulfides (H2Sn) have recently been identified as signaling molecules that mediate the activation of ion channels, regulation of tumor growth, and the transcriptional regulation of oxidative stress; some of which were previously ascribed to H2S. Cystathionine β-synthetase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are known as H2S-producing enzymes. 3MST also produces H2Sn and other persulfurated molecules such as cysteine persulfide, glutathione persulfide, and persulfurated proteins. The chemical interaction of H2S and nitric oxide (NO) also produces H2Sn, which may be the mechanism underlying the synergistic effect of H2S and NO that was initially reported on vascular relaxation. H2Sn and other persulfurated molecules elicit their effect via S-sulfuration (S-sulfhydration) of specific cysteine residues of the target proteins. This review article focuses on the production and roles of H2Sn as well as H2S in the central nervous system.