RT Journal Article
T1 Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration
A1 Aguareles Gorines, José
A1 Paraíso Luna, Juan
A1 Palomares, Belen
A1 Bajo Grañeras, Raquel
A1 Navarrete, Carmen
A1 Ruiz Calvo, Andrea
A1 García Rincón, Daniel
A1 García Taboada, Elena
A1 Guzmán Pastor, Manuel
A1 Muñoz, Eduardo
A1 Galve Roperh, Ismael
AB Background: The administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropic activity, including CB2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids.Methods: We investigated the pro-neurogenic potential of the synthetic cannabigerol derivative, VCE-003.2, in striatal neurodegeneration by using adeno-associated viral expression of mutant huntingtin in vivo and mouse embryonic stem cell differentiation in vitro.Results: Oral administration of VCE-003.2 protected striatal medium spiny neurons from mutant huntingtin-induced damage, attenuated neuroinflammation and improved motor performance. VCE-003.2 bioavailability was characterized and the potential undesired side effects were evaluated by analyzing hepatotoxicity after chronic treatment. VCE-003.2 promoted subventricular zone progenitor mobilization, increased doublecortin-positive migrating neuroblasts towards the injured area, and enhanced effective neurogenesis. Moreover, we demonstrated the proneurogenic activity of VCE-003.2 in embryonic stem cells. VCE-003.2 was able to increase neuroblast formation and striatal-like CTIP2-mediated neurogenesis.Conclusions: The cannabigerol derivative VCE-003.2 improves subventricular zone-derived neurogenesis in response to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration.
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/91122
UL https://hdl.handle.net/20.500.14352/91122
LA eng
NO Aguareles J., Paraíso-Luna J., Palomares B., Bajo-Grañeras R., Navarrete C., Ruiz-Calvo A., García-Rincón, D., García-Taboada E., Guzmán M., Muñoz E., Galve-Roperh I. Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration. Translational Neurodegeneration 8:9 (2019).
NO Ministerio de Economía y Competitividad (España)
DS Docta Complutense
RD 9 abr 2025