Abstract
Hydrogen sulfide (H(2)S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H(2)S in neurodegenerative diseases may be mediated by N-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H(2)S while minimizing its toxicity, we synthesized a series of H(2)S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP(+))-induced cell death, a cellular model of Parkinson's disease. We observed that cytoprotective effect of H(2)S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H(2)S, levels. These studies suggest that H(2)S-donor compounds that increase intracellular sulfane sulfur are potentially useful neuroprotective agents against neurodegenerative diseases.