| Summary: | Spinal cord injury affects the lives of millions of people around the world, often causing disability and, in unfortunate circumstances, death. Rehabilitation can partly improve outcomes and only a small percentage of patients, typically the least injured, can hope to return to normal living conditions. <i>Cannabis sativa</i> is gaining more and more interest in recent years, even though its beneficial properties have been known for thousands of years. Cannabigerol (CBG), extracted from <i>C. sativa</i>, is defined as the “mother of all cannabinoids” and its properties range from anti-inflammatory to antioxidant and neuroprotection. Using NSC-34 cells to model spinal cord injury in vitro, our work evaluated the properties of CBG treatments in motor neuron regeneration. While pre-treatment can modulate oxidative stress and increase antioxidant enzyme genes, such as <i>Tnx1</i>, decreasing <i>Nos1</i> post-treatment seems to induce regeneration genes by triggering different pathways, such as <i>Gap43</i> via p53 acetylation by <i>Ep300</i> and <i>Ddit3</i> and <i>Xbp1</i> via <i>Bdnf</i> signaling, along with cytoskeletal remodeling signaling genes <i>Nrp1</i> and <i>Map1b</i>. Our results indicate CBG as a phytocompound worth further investigation in the field of neuronal regeneration.
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