Hydrogen sulfide/polysulfides signaling and neuronal diseases
Hideo Kimura
Abstract
<h2>Abstract</h2> Hydrogen sulfide (H<sub>2</sub>S) and polysulfides including H<sub>2</sub>S<sub>n</sub> (n = 2 or more) regulate neuronal activity, vascular tone, oxytosis/ferroptosis, oxygen sensing, cancer growth and senescence. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) produce H<sub>2</sub>S. Polysulfides are also produced by various enzymes including 3MST. In addition, transient receptor potential ankyrin 1 (TRPA1) channel-an important polysulfide target-modulates sulfur metabolism (including cysteine, H<sub>2</sub>S and polysulfides) and also affects the neurotransmitter GABA. Polysulfides persulfidate the cysteine residues of the target proteins, causing conformational changes that alter their activity. By contrast, H<sub>2</sub>S persulfidates oxidized cysteine residues (e.g., S-nitrosylated- and S-sulfinated) in its targets. H<sub>2</sub>S/polysulfides protect neurons from oxidative stress and thereby protect cells against various forms of cell death including oxytosis and ferroptosis. A deviation from normal H<sub>2</sub>S and polysulfides levels has been suggested to play a role in the pathophysiology of various neuronal- and psychiatric diseases.