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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4949444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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