Publication:
VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease.

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Date

2016-06-24

Authors

Diaz-Alonso, Javier
Paraiso-Luna, Juan
Navarrete, Carmen
Del Rio, Carmen
Cantarero, Irene
Palomares, Belen
Aguareles, Jose
Fernandez-Ruiz, Javier
Bellido, Maria Luz
Pollastro, Federica

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Nature Publishing Group
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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.

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MeSH Terms

Animals
Cannabinoids
Cell differentiation
Cell line
Cell line, tumor
Cell survival
Cells, cultured
Disease models, animal
Gene expression
HEK293 cells
Humans
Huntington disease
Male

DeCS Terms

Células cultivadas
Células HEK293
Diferenciación celular
Enfermedad de Huntington
Expresión génica
Línea celular tumoral
Modelos animales de enfermedad
Supervivencia celular

CIE Terms

Keywords

Mesenchymal stem cells, Mice, inbred C57BL, Neural stem cells, Neuroprotective agents, Quinones, Rats

Citation

Díaz-Alonso J, Paraíso-Luna J, Navarrete C, Del Río C, Cantarero I, Palomares B, et al. VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease. Sci Rep. 2016 Jul 19;6:29789