RT Journal Article
T1 VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease.
A1 Diaz-Alonso, Javier
A1 Paraiso-Luna, Juan
A1 Navarrete, Carmen
A1 Del Rio, Carmen
A1 Cantarero, Irene
A1 Palomares, Belen
A1 Aguareles, Jose
A1 Fernandez-Ruiz, Javier
A1 Bellido, Maria Luz
A1 Pollastro, Federica
A1 Appendino, Giovanni
A1 Calzado, Marco A
A1 Galve-Roperh, Ismael
A1 Muñoz, Eduardo
K1 Mesenchymal stem cells
K1 Mice, inbred C57BL
K1 Neural stem cells
K1 Neuroprotective agents
K1 Quinones
K1 Rats
AB 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.
PB Nature Publishing Group
YR 2016
FD 2016-06-24
LK http://hdl.handle.net/10668/10280
UL http://hdl.handle.net/10668/10280
LA en
NO 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
NO This work was supported by the MINECO grant RTC-2015-3364 to MLB, CNR, EM and IGR cofounded by the European Development Regional Fund in the Framework of the Operative Program “Reinforcement of research,technological development and innovation”. EM was also supported by the MINECO grant SAF2014-53763-P and IGR by grant PI15-00310 supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016)and S2011/BMD2336 cofinanced by the European Development Regional Fund “A way to achieve Europe”. JPL was supported by FPU program fellowship (Ministerio de Educación, Cultura y Deporte) and NeuroStemCMS2011/BMD2336. JA was supported by RTC-2015-3364. We acknowledge Carmen Cabrero-Doncel for her assistance with the article and Andrea Ruiz-Calvo for assistance in striatal cell culture experiments
DS RISalud
RD Apr 5, 2025