Instituto Universitario de Investigación en Neuroquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
Br J Pharmacol. 2021 Mar;178(6):1373-1387. doi: 10.1111/bph.15386. Epub 2021 Feb 20.
Cannabinoids form a singular group of plant-derived compounds, endogenous lipids and synthetic derivatives with multiple therapeutic effects exerted by targeting different elements of the endocannabinoid system. One of their therapeutic applications is the preservation of neuronal integrity exerted by attenuating the multiple neurotoxic events that kill neurons in neurodegenerative disorders. In this review, we will address the potential of cannabinoids as neuroprotective agents in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder characterized by muscle denervation, atrophy and paralysis, and progressive deterioration in upper and/or lower motor neurons. The emphasis will be paid on the cannabinoid type 2 (CB ) receptor, whose activation limits glial reactivity, but the potential of additional endocannabinoid-related targets will be also addressed. The evidence accumulated so far at the preclinical level supports the need to soon move towards the patients and initiate clinical trials to confirm the potential of cannabinoid-based medicines as disease modifiers in ALS. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc.
大麻素是一组独特的植物衍生化合物、内源性脂质和合成衍生物，通过针对内源性大麻素系统的不同元件发挥多种治疗作用。它们的治疗应用之一是通过减轻在神经退行性疾病中杀死神经元的多种神经毒性事件来保持神经元的完整性。在这篇综述中，我们将讨论大麻素作为肌萎缩侧索硬化症（ALS）神经保护剂的潜力，ALS 是一种毁灭性的神经退行性疾病，其特征是肌肉去神经支配、萎缩和瘫痪，以及上下运动神经元的进行性恶化。重点将放在大麻素类型 2（CB2）受体上，其激活限制了神经胶质反应，但也将涉及其他内源性大麻素相关靶点的潜力。迄今为止在临床前水平积累的证据支持我们需要尽快转向患者并启动临床试验，以确认基于大麻素的药物作为 ALS 疾病修饰剂的潜力。
