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Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

机译：大麻素药理/治疗慢性退行性疾病影响中枢神经系统的疾病

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The endocannabinoid system (ECS) exerts a modulatory effect of important functions such as neurotransmission, glial activation, oxidative stress, or protein homeostasis. Dysregulation of these cellular processes is a common neuropathological hallmark in aging and in neurodegenerative diseases of the central nervous system (CNS). The broad spectrum of actions of cannabinoids allows targeting different aspects of these multifactorial diseases. In this review, we examine the therapeutic potential of the ECS for the treatment of chronic neurodegenerative diseases of the CNS focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. First, we describe the localization of the molecular components of the ECS and how they are altered under neurodegenerative conditions, either contributing to or protecting cells from degeneration. Second, we address recent advances in the modulation of the ECS using experimental models through different strategies including the direct targeting of cannabinoid receptors with agonists or antagonists, increasing the endocannabinoid tone by the inhibition of endocannabinoid hydrolysis, and activation of cannabinoid receptor independent effects. Preclinical evidence indicates that cannabinoid pharmacology is complex but supports the therapeutic potential of targeting the ECS. Third, we review the clinical evidence and discuss the future perspectives on how to bridge human and animal studies to develop cannabinoid-based therapies for each neurodegenerative disorder. Finally, we summarize the most relevant opportunities of cannabinoid pharmacology related to each disease and the multiple unexplored pathways in cannabinoid pharmacology that could be useful for the treatment of neurodegenerative diseases.
机译：Endocannabinoid系统（ECS）施加重要功能的调节效果，如神经递血，神经胶激，氧化胁迫，或蛋白质稳态。这些细胞方法的失调是在中枢神经系统（CNS）的衰老和神经变性疾病中的常见神经病理学标志。大麻素的广谱作用允许靶向这些多因素疾病的不同方面。在本综述中，我们研究了ECS治疗CNS的慢性神经变性疾病的治疗潜力，重点是阿尔茨海默病，帕金森病，亨廷顿的疾病和肌萎缩的侧面硬化。首先，我们描述ECS的分子组分的定位以及它们在神经变性条件下改变的定位，无论是为来自变性的细胞的贡献还是保护细胞。其次，我们通过不同的策略解决了近期ECS调制ECS的进展，包括用激动剂或拮抗剂的直接靶向加麻素受体的直接靶向，通过抑制内突植物水解，增加了内胆碱蛋白质水解的激活。临床前证据表明大麻素药理复杂，但支持靶向ECS的治疗潜力。第三，我们审查了临床证据，并讨论了如何弥合如何弥合人类和动物研究以开发每种神经变性疾病的大麻疗法的疗法。最后，我们总结了大麻药物与每种疾病相关的最相关的机会，以及大麻素药理学中的多种未探究途径，可用于治疗神经变性疾病。

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