Hydrogen Sulfide: Modern Roles of an Ancient Signaling Molecule in Neuronal Function

Abstract

Life evolved in a hydrogen sulfide (H2S)-rich environment, eons ago, and with it emerged signal transduction cascades modulated by sulfhydration. Sulfhydration/persulfidation is a newly discovered posttranslational modification, wherein the -SH groups of reactive cysteine residues are converted to -SSH or persulfide groups. Sulfhydration modulates diverse physiological processes, ranging from response to inflammation to neuroprotection. H2S is generated via the reverse transsulfuration pathway in mammals from the amino acid cysteine and our studies reveal that this pathway is disrupted in aging and in neurodegenerative diseases such as Huntington’s disease, Parkinson’s disease and Alzheimer’s disease. Accordingly, targeting the reverse transsulfuration, may afford therapeutic benefits in neurodegenerative disorders involving imbalanced cysteine and H2S metabolism.