RT journal article
T1 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation
A1 Geribaldi Doldán, Noelia
A1 Flores Giubi, Eugenia
A1 Murillo Carretero, Maribel
A1 García Bernal, Francisco
A1 Domínguez Riscart, Jesús
A1 Verástegui Escolano, Cristina
A1 Hernández Galán, Rosario
A1 Castro González, Carmen
A1 Carrasco Viñuela, Manuel
A1 Macías Sánchez, Antonio José
A2 Química Orgánica
K1 12-deoxyphorbol
K1 prostratin
K1 PKC
K1 neurogenesis
K1 neural progenitor cells
AB 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 tounderstand 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 neuralprogenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exertsa proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase Cinhibitor 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 thehippocampus 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.
PB International Journal of Neuropsychopharmacology
YR 2015
FD 2015-07
LK http://hdl.handle.net/10498/20338
UL http://hdl.handle.net/10498/20338
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 06-nov-2026