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Here we demonstrate that Cdk5 is activated by S-nitrosylation or reaction of nitric oxide (NO)-related species with the thiol groups of cysteine residues 83 and 157, to form SNO-Cdk5. We then show that S-nitrosylation of Cdk5 contributes to amyloid-\u03b2 (A\u03b2) peptide-induced dendritic spine loss. Furthermore, we observed significant levels of SNO-Cdk5 in postmortem Alzheimer\u2019s disease (AD) but not in normal human brains. These findings suggest that S-nitrosylation of Cdk5 is an aberrant regulatory mechanism of enzyme activity that may contribute to the pathogenesis of AD.<\/jats:p>","DOI":"10.1073\/pnas.1105172108","type":"journal-article","created":{"date-parts":[[2011,8,16]],"date-time":"2011-08-16T04:34:54Z","timestamp":1313469294000},"page":"14330-14335","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":175,"title":["S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by \u03b2-amyloid peptide"],"prefix":"10.1073","volume":"108","author":[{"given":"Jing","family":"Qu","sequence":"first","affiliation":[{"name":"Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Del E. 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