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

Identificadores del recurso

http://hdl.handle.net/10498/20338

10.1093/ijnp/pyv085

Procedència

(Repositorio de Objetos de Docencia e Investigación: RODIN)

Fitxa

Títol:: 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation
Tema:: 12-deoxyphorbol; prostratin; PKC; neurogenesis; neural progenitor cells
Descripció:: 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.
Font:: International Journal of Neuropsychopharmacology, 2016, 1–14
Idioma:: English
Autor/Productor:: Geribaldi Doldán, Noelia; Flores Giubi, Eugenia; Murillo Carretero, Maribel; García Bernal, Francisco; Domínguez-Riscart, Jesús; Verástegui Escolano, Cristina; Hernández Galán, Rosario; Castro González, Carmen; Carrasco Viñuela, Manuel; Macías Sánchez, Antonio José
Editor:: International Journal of Neuropsychopharmacology
Otros colaboradores/productores:: Química Orgánica
Drets:: Attribution-NonCommercial-NoDerivatives 4.0 Internacional; info:eu-repo/semantics/openAccess; http://creativecommons.org/licenses/by-nc-nd/4.0/
Data:: 2018-04-18T07:10:50Z; 2015-07
Tipo de recurso:: journal article
Format:: application/pdf

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1. <dc:title>12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation</dc:title>
2. <dc:creator>Geribaldi Doldán, Noelia</dc:creator>
3. <dc:creator>Flores Giubi, Eugenia</dc:creator>
4. <dc:creator>Murillo Carretero, Maribel</dc:creator>
5. <dc:creator>García Bernal, Francisco</dc:creator>
6. <dc:creator>Domínguez-Riscart, Jesús</dc:creator>
7. <dc:creator>Verástegui Escolano, Cristina</dc:creator>
8. <dc:creator>Hernández Galán, Rosario</dc:creator>
9. <dc:creator>Castro González, Carmen</dc:creator>
10. <dc:creator>Carrasco Viñuela, Manuel</dc:creator>
11. <dc:creator>Macías Sánchez, Antonio José</dc:creator>
12. <dc:contributor>Química Orgánica</dc:contributor>
13. <dc:subject>12-deoxyphorbol</dc:subject>
14. <dc:subject>prostratin</dc:subject>
15. <dc:subject>PKC</dc:subject>
16. <dc:subject>neurogenesis</dc:subject>
17. <dc:subject>neural progenitor cells</dc:subject>
18. <dc:description>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.</dc:description>
19. <dc:date>2018-04-18T07:10:50Z</dc:date>
20. <dc:date>2018-04-18T07:10:50Z</dc:date>
21. <dc:date>2015-07</dc:date>
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30. <dc:publisher>International Journal of Neuropsychopharmacology</dc:publisher>
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