Journal
MEDCHEMCOMM
Volume 5, Issue 10, Pages 1577-1583Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4md00180j
Keywords
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Funding
- National Institutes of Health (NIH) [HL101930]
- ACS-Teva USA Scholar Award
- NIH [HL116571]
- Grants-in-Aid for Scientific Research [26104509] Funding Source: KAKEN
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Hydrogen sulfide (H2S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H2S in neurodegenerative diseases may be mediated by N-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H2S while minimizing its toxicity, we synthesized a series of H2S-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 effects of H2S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H2S, levels. These studies suggest that H2S-donor compounds that increase intracellular sulfane sulfur levels are potentially useful neuroprotective agents against neurodegenerative diseases.
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