Logotipo ImpactU
Autor

ELAC (3,12‐di‐O‐acetyl‐8‐O‐tigloilingol), a plant‐derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCβ activation

Acceso Abierto
ID Minciencias: ART-0000412619-45
Ranking: ART-ART_A1

Abstract:

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.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.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.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.

Tópico:

Bioactive Natural Diterpenoids Research

Citaciones:

Citations: 29
29

Citaciones por año:

Altmétricas:

Paperbuzz Score: 0
0

Información de la Fuente:

SCImago Journal & Country Rank
FuenteBritish Journal of Pharmacology
Cuartil año de publicaciónNo disponible
Volumen174
Issue14
Páginas2373 - 2392
pISSNNo disponible
ISSN0007-1188

Enlaces e Identificadores:

Artículo de revista