12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

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12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

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dc.contributor.author Geribaldi-Doldán, Noelia
dc.contributor.author Flores-Giubi, Eugenia
dc.contributor.author Murillo-Carretero, Maribel
dc.contributor.author García-Bernal, Francisco
dc.contributor.author Domínguez-Riscart, Jesús
dc.contributor.author Verástegui, Cristina
dc.contributor.author Hernández-Galán, Rosario
dc.contributor.author Castro, Carmen
dc.contributor.author Carrasco Viñuela, Manuel
dc.contributor.author Macias Sánchez, Antonio José
dc.contributor.other Química Orgánica en_US
dc.date.accessioned 2018-04-18T07:10:50Z
dc.date.available 2018-04-18T07:10:50Z
dc.date.issued 2015-07
dc.identifier.uri http://hdl.handle.net/10498/20338
dc.description.abstract Background: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. Methodology: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. Results: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. en_US
dc.format application/pdf en_US
dc.language.iso eng en_US
dc.publisher International Journal of Neuropsychopharmacology en_US
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 Internacional *
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ *
dc.source International Journal of Neuropsychopharmacology, 2016, 1–14 en_US
dc.subject 12-deoxyphorbol en_US
dc.subject prostratin en_US
dc.subject PKC en_US
dc.subject neurogenesis en_US
dc.subject neural progenitor cells en_US
dc.title 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation en_US
dc.type info:eu-repo/semantics/article en_US
dc.identifier.doi 10.1093/ijnp/pyv085

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internacional