Gasotransmitter hydrogen sulfide signaling in neuronal health and disease

Hydrogen sulfide is a gaseous signaling molecule or gasotransmitter which plays important roles in a wide spectrum of physiologic processes in the brain and peripheral tissues. Unlike nitric oxide and carbon monoxide, the other major gasotransmitters, research on hydrogen sulfide is still in its infancy. One of the modes by which hydrogen sulfide signals is via a posttranslational modification termed sulfhydration/persulfidation, which occurs on reactive cysteine residues on target proteins, where the reactive SH group is converted to an SSH group. Sulfhydration is a substantially prevalent modification, which modulates the structure or function of proteins being modified. Thus, precise control of endogenous hydrogen sulfide production and metabolism is critical for maintenance of optimal cellular function, with excess generation and paucity, both contributing to pathology. Dysregulation of the reverse transsulfuration pathway which generates hydrogen sulfide occurs in several neurodegenerative diseases such as Parkinson's disease, Huntington's disease and Alzheimer's disease. Accordingly, treatment with donors of hydrogen sulfide or stimulation of the reverse transsulfuration have proved beneficial in several neurodegenerative states. In this review we focus on hydrogen sulfide mediated neuronal signaling processes that contribute to neuroprotection.