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Title: VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease.
Authors: Díaz-Alonso, Javier
Paraíso-Luna, Juan
Navarrete, Carmen
Del Río, Carmen
Cantarero, Irene
Palomares, Belén
Aguareles, José
Fernández-Ruiz, Javier
Bellido, María Luz
Pollastro, Federica
Appendino, Giovanni
Calzado, Marco A
Galve-Roperh, Ismael
Muñoz, Eduardo
metadata.dc.subject.mesh: Animals
Cell Differentiation
Cell Line
Cell Line, Tumor
Cell Survival
Cells, Cultured
Disease Models, Animal
Gene Expression
HEK293 Cells
Huntington Disease
Mesenchymal Stem Cells
Mice, Inbred C57BL
Neural Stem Cells
Neuroprotective Agents
Issue Date: 19-Jul-2016
Abstract: Cannabinoids have shown to exert neuroprotective actions in animal models by acting at different targets including canonical cannabinoid receptors and PPARγ. We previously showed that VCE-003, a cannabigerol (CBG) quinone derivative, is a novel neuroprotective and anti-inflammatory cannabinoid acting through PPARγ. We have now generated a non-thiophilic VCE-003 derivative named VCE-003.2 that preserves the ability to activate PPARγ and analyzed its neuroprotective activity. This compound exerted a prosurvival action in progenitor cells during neuronal differentiation, which was prevented by a PPARγ antagonist, without affecting neural progenitor cell proliferation. In addition, VCE-003.2 attenuated quinolinic acid (QA)-induced cell death and caspase-3 activation and also reduced mutant huntingtin aggregates in striatal cells. The neuroprotective profile of VCE-003.2 was analyzed using in vivo models of striatal neurodegeneration induced by QA and 3-nitropropionic acid (3NP) administration. VCE-003.2 prevented medium spiny DARPP32(+) neuronal loss in these Huntington's-like disease mice models improving motor deficits, reactive astrogliosis and microglial activation. In the 3NP model VCE-003.2 inhibited the upregulation of proinflammatory markers and improved antioxidant defenses in the brain. These data lead us to consider VCE-003.2 to have high potential for the treatment of Huntington's disease (HD) and other neurodegenerative diseases with neuroinflammatory traits.
metadata.dc.identifier.doi: 10.1038/srep29789
Appears in Collections:Producción 2020

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