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Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3β phosphorylation
National Eye Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
National Eye Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
National Eye Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
National Eye Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
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2010 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 207, no 4, 867-880 p.Article in journal (Refereed) Published
Abstract [en]

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 3beta (GSK3beta) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine-induced Parkinson's 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 GSK3beta 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-PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions.

Place, publisher, year, edition, pages
The Rockefeller University Press , 2010. Vol. 207, no 4, 867-880 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-125644DOI: 10.1084/jem.20091704ISI: 000276552700017PubMedID: 20231377OAI: oai:DiVA.org:uu-125644DiVA: diva2:320514
Available from: 2010-05-25 Created: 2010-05-25 Last updated: 2017-12-12Bibliographically approved

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