Casares, LauraUnciti-Broceta, Juan DiegoPrados, Maria EugeniaCaprioglio, DiegoMattoteia, DaianaHiggins, MaureenApendino, GiovanniDinkova-Kostova, Albena TMuñoz, Eduardode la Vega, Laureano2023-02-092023-02-092020-08-22Casares L, Unciti-Broceta JD, Prados ME, Caprioglio D, Mattoteia D, Higgins M, et al. Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity. Redox Biol. 2020 Oct;37:101689http://hdl.handle.net/10668/16178Oxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington's disease, setting the basis for further developments in vivo.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Cannabidiol derivative/ NRF2/ BACH1/ HMOX1/ neurodegenerative diseasesMiceNF-E2-related factor 2Neurodegenerative diseasesOxidative stressAnimalsAntioxidantsBasic-Leucine Zipper Transcription FactorsCell LineDisease Models, Animalresearch article32863231open accessAnimalesAntioxidantesFactores de transcripción con cremalleras de leucina de carácter básicoLínea celularModelos animales de enfermedad10.1016/j.redox.2020.1016892213-2317PMC7476313https://doi.org/10.1016/j.redox.2020.101689https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476313/pdf