OBJECTIVEThis review discusses the current status and progress in studies on the roles of hydrogen sulfide (H(2)S) in regulation of neurotoxicity, neuroprotection, and neuromodulator, as well as its therapeutic potential for neurodegenerative disorders.

DATA SOURCESThe data used in this review were mainly from Medline and PubMed published in English from 2001 to August 2011. The search terms were "hydrogen sulfide", "neuron", and "neurodegenerative disorders".

STUDY SELECTIONArticles regarding the regulation of neuronal function, the protection against neuronal damage and neurological diseases, and their possible cellular and molecular mechanisms associated with H(2)S were selected.

RESULTSThe inhibited generation of endogenous H(2)S is implicated in 1-methy-4-phenylpyridinium ion, 6-OHDA, and homocysteine-triggered neurotoxicity. H(2)S elicits neuroprotection in Alzheimer's disease and Parkinson's disease models as well as protecting neurons against oxidative stress, ischemia, and hypoxia-induced neuronal death. H(2)S offers anti-oxidant, anti-inflammatory and anti-apoptotic effects, as well as activates ATP-sensitive potassium channels and cystic fibrosis transmembrane conductance regulator Cl- channels. H(2)S regulates the long-term potentiation (LTP) and GABAB receptors in the hippocampus, as well as intracellular calcium and pH homeostasis in neurons and glia cells.

CONCLUSIONSThese articles suggest that endogenous H(2)S may regulate the toxicity of neurotoxin. H(2)S not only acts as a neuroprotectant but also serves as a novel neuromodulator.