RT journal article
T1 ELAC (3,12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCβ activation
A1 Murillo Carretero, María Isabel
A1 Geribaldi Doldán, Noelia
A1 Flores Giubi, Eugenia
A1 García Bernal, Francisco
A1 Navarro Quiroz, Elkin A
A1 Carrasco Viñuela, Manuel
A1 Macías Sánchez, Antonio José
A1 Herrero Foncubierta, Pilar
A1 Delgado Ariza, Antonio
A1 Verástegui Escolano, Cristina
A1 Domínguez Riscart, Jesús
A1 Daoubi, Mourad
A1 Hernández Galán, Rosario
A1 Castro González, Carmen
A2 Anatomía y Embriología Humana
A2 BiomedicinaBiotecnología y Salud Pública
A2 Química Orgánica
AB Background and Purpose: Pharmacological strategies aimed to facilitate neuronal renewal in the adult brain, by promoting endogenous neurogenesis, constitute promising therapeutic options for pathological or traumatic brain lesions. We have previously shown that non-tumour-promoting PKC-activating compounds (12-deoxyphorbols) promote adult neural progenitor cell (NPC) proliferation in vitro and in vivo, enhancing the endogenous neurogenic response of the brain to a traumatic injury. Here, we show for the first time that a diterpene with a lathyrane skeleton can also activate PKC and promote NPC proliferation. Experimental Approach: We isolated four lathyranes from the latex of Euphorbia plants and tested their effect on postnatal NPC proliferation, using neurosphere cultures. The bioactive lathyrane ELAC (3,12-di-O-acetyl-8-O-tigloilingol) was also injected into the ventricles of adult mice to analyse its effect on adult NPC proliferation in vivo. Key Results: The lathyrane ELAC activated PKC and significantly increased postnatal NPC proliferation in vitro, particularly in synergy with FGF2. In addition ELAC stimulated proliferation of NPC, specifically affecting undifferentiated transit amplifying cells. The proliferative effect of ELAC was reversed by either the classical/novel PKC inhibitor Gö6850 or the classical PKC inhibitor Gö6976, suggesting that NPC proliferation is promoted in response to activation of classical PKCs, particularly PKCß. ELAC slightly increased the proportion of NPC expressing Sox2. The effects of ELAC disappeared upon acetylation of its C7-hydroxyl group. Conclusions and Implications: We propose lathyranes like ELAC as new drug candidates to modulate adult neurogenesis through PKC activation. Functional and structural comparisons between ELAC and phorboids are included.
PB John Wiley and Sons Inc.
SN 1476-5381
YR 2017
FD 2017
LK http://hdl.handle.net/10498/34181
UL http://hdl.handle.net/10498/34181
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 05-nov-2026