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dc.contributor.authorGeribaldi-Doldán, Noelia
dc.contributor.authorFlores-Giubi, Eugenia
dc.contributor.authorMurillo-Carretero, Maribel
dc.contributor.authorGarcía-Bernal, Francisco
dc.contributor.authorDomínguez-Riscart, Jesús
dc.contributor.authorVerástegui, Cristina
dc.contributor.authorHernández-Galán, Rosario
dc.contributor.authorCastro, Carmen
dc.contributor.authorCarrasco Viñuela, Manuel
dc.contributor.authorMacias Sánchez, Antonio José
dc.contributor.otherQuímica Orgánicaen_US
dc.date.accessioned2018-04-18T07:10:50Z
dc.date.available2018-04-18T07:10:50Z
dc.date.issued2015-07
dc.identifier.urihttp://hdl.handle.net/10498/20338
dc.description.abstractBackground: 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.formatapplication/pdfen_US
dc.language.isoengen_US
dc.publisherInternational Journal of Neuropsychopharmacologyen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.sourceInternational Journal of Neuropsychopharmacology, 2016, 1–14en_US
dc.subject12-deoxyphorbolen_US
dc.subjectprostratinen_US
dc.subjectPKCen_US
dc.subjectneurogenesisen_US
dc.subjectneural progenitor cellsen_US
dc.title12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activationen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.identifier.doi10.1093/ijnp/pyv085


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This work is under a Creative Commons License Attribution-NonCommercial-NoDerivatives 4.0 Internacional