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, José
A1 Paraíso-Luna, Juan
A1 Palomares, Belén
A1 Bajo-Grañeras, Raquel
A1 Navarrete, Carmen
A1 Ruiz-Calvo, Andrea
A1 García-Rincón, Daniel
A1 García-Taboada, Elena
A1 Guzmán, Manuel
A1 Muñoz, Eduardo
A1 Galve-Roperh, Ismael
K1 Cannabinoid
K1 Huntingtin
K1 Neurodegeneration
K1 Neurogenesis
K1 PPAR
AB 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. 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. 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. The cannabigerol derivative VCE-003.2 improves subventricular zone-derived neurogenesis in response to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration.
SN 2047-9158
YR 2019
FD 2019-03-08
LK https://hdl.handle.net/10668/25794
UL https://hdl.handle.net/10668/25794
LA en
DS RISalud
RD Apr 17, 2025