{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:37:55Z","timestamp":1792712275718,"version":"4.5.0"},"reference-count":32,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,4,12]]},"abstract":"<jats:p>Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3\u03b2 (GSK3\u03b2) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine\u2013induced Parkinson\u2019s dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency\/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3\u03b2 phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC\u2013PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions.<\/jats:p>","DOI":"10.1084\/jem.20091704","type":"journal-article","created":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T23:50:33Z","timestamp":1268697033000},"page":"867-880","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":109,"title":["Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3\u03b2 phosphorylation"],"prefix":"10.1084","volume":"207","author":[{"given":"Zhongshu","family":"Tang","sequence":"first","affiliation":[{"name":"National Eye Institute, National Institutes of Health (NIH), Bethesda, MD 20892 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pachiappan","family":"Arjunan","sequence":"additional","affiliation":[{"name":"National Eye Institute, National Institutes of Health (NIH), 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