Department of Excellence of Biotechnology, Chemistry and Pharmacy, University of Siena, Via A. Moro, 2, 53100, Siena, Italy.
Department of Excellence of Pharmacy, University of Naples Federico II, Via D. Montesano, 49, 80131, Naples, Italy.
ChemMedChem. 2020 Nov 4;15(21):1985-2003. doi: 10.1002/cmdc.202000310. Epub 2020 Sep 10.
Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system. At present, there is no definitive cure, and the few available disease-modifying options display either poor efficacy or life-threatening side effects. There is clear evidence that relapsing-remitting clinical attacks in MS are driven by inflammatory demyelination and that the subsequent disease steps, being irresponsive to immunotherapy, result from neurodegeneration. The endocannabinoid system (ECS) stands halfway between three key pathomechanisms underlying MS, namely inflammation, neurodegeneration and oxidative stress, thus representing a kingpin for the identification of novel therapeutic targets in MS. This review summarizes the current state of the art in the field of endocannabinoid metabolism modulators and their in vivo effects on relevant animal models. We also highlight key molecular underpinnings of their therapeutic efficacy as well as the potential to turn them into promising clinical candidates.
多发性硬化症（MS）是一种中枢神经系统的慢性、免疫介导的疾病。目前，尚无明确的治愈方法，少数可用的疾病修饰治疗方法要么疗效不佳，要么有生命危险的副作用。有明确的证据表明，MS 中的复发缓解型临床发作是由炎症性脱髓鞘引起的，随后的疾病进展对免疫疗法无反应，是由神经退行性变引起的。内源性大麻素系统（ECS）处于 MS 三种关键发病机制的中间位置，即炎症、神经退行性变和氧化应激，因此是确定 MS 中新型治疗靶点的关键因素。这篇综述总结了内源性大麻素代谢调节剂在该领域的最新进展及其对相关动物模型的体内作用。我们还强调了它们治疗效果的关键分子基础以及将它们转化为有前途的临床候选药物的潜力。
