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Hydrogen sulfide (H2S) used to be known as a toxic gas. However, in the last two decades, accumulating evidence has revealed its role as a bioactive molecule in the biological systems. H2S has relatively high expression in the brain, exerting multiple functions in both health and diseases. It modulates neurotransmission by influencing behaviors of NMDA receptors and second messenger systems including intracellular Ca(2+) concentration and intracellular cAMP levels and so forth. H2S shows potential therapeutic value in several CNS diseases including Alzheimer's disease, Parkinson's disease, ischemic stroke, and traumatic brain injury. As a neuroprotectant, H2S produces antioxidant, anti-inflammatory, and antiapoptotic effects in pathological situations. Sulfhydration of target proteins is an important mechanism underlying these effects. This Review summarizes the current understanding of H2S in the central nervous system, with emphasis on its role as a neuromodulator and a neuroprotectant.

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