Instituto Universitario de Investigación en Neuroquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Br J Pharmacol. 2019 May;176(10):1370-1383. doi: 10.1111/bph.14382. Epub 2018 Jul 8.
At the beginning of the 21st century, the therapeutic management of neurodegenerative disorders remains a major biomedical challenge, particularly given the worldwide ageing of the population over the past 50 years that is expected to continue in the forthcoming years. This review will focus on the promise of cannabinoid-based therapies to address this challenge. This promise is based on the broad neuroprotective profile of cannabinoids, which may cooperate to combat excitotoxicity, oxidative stress, glia-driven inflammation and protein aggregation. Such effects may be produced by the activity of cannabinoids through their canonical targets (e.g. cannabinoid receptors and endocannabinoid enzymes) and also via non-canonical elements and activities in distinct cell types critical for cell survival or neuronal replacement (e.g. neurons, glia and neural precursor cells). Ultimately, the therapeutic events driven by endocannabinoid signalling reflect the activity of an endogenous system that regulates the preservation, rescue, repair and replacement of neurons and glia. LINKED ARTICLES: This article is part of a themed section on 8 European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.
在 21 世纪初,神经退行性疾病的治疗管理仍然是一个主要的生物医学挑战,特别是考虑到过去 50 年来全球人口的老龄化,预计这种情况在未来几年还将继续。这篇综述将重点介绍基于大麻素的疗法在应对这一挑战方面的前景。这一前景是基于大麻素广泛的神经保护特性,大麻素可能协同对抗兴奋性毒性、氧化应激、胶质细胞驱动的炎症和蛋白质聚集。这种作用可能是通过大麻素的活性产生的,这些活性通过它们的典型靶点(例如大麻素受体和内源性大麻素酶),以及通过不同细胞类型中的非典型元素和活性来实现,这些细胞类型对细胞存活或神经元替代至关重要(例如神经元、神经胶质细胞和神经前体细胞)。最终,内源性大麻素信号驱动的治疗事件反映了一个内源性系统的活动,该系统调节神经元和神经胶质细胞的保存、挽救、修复和替代。相关文章:本文是关于 8 届欧洲大麻素研究研讨会的专题部分的一部分。要查看该部分中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc/。