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

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 actin...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949444/
https://www.ncbi.nlm.nih.gov/pubmed/27430371
http://dx.doi.org/10.1038/srep29789
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author 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
author_facet 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
author_sort Díaz-Alonso, Javier
collection PubMed
description 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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spelling pubmed-49494442016-07-26 VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease 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 Sci Rep Article 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. Nature Publishing Group 2016-07-19 /pmc/articles/PMC4949444/ /pubmed/27430371 http://dx.doi.org/10.1038/srep29789 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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
VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease
title VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease
title_full VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease
title_fullStr VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease
title_full_unstemmed VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease
title_short VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington’s disease
title_sort vce-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of huntington’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949444/
https://www.ncbi.nlm.nih.gov/pubmed/27430371
http://dx.doi.org/10.1038/srep29789
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