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大麻素在神经退行性疾病中的治疗潜力:一项选择性综述。

Therapeutic potential of cannabinoids in neurodegenerative disorders: a selective review.

作者信息

Velayudhan Latha, Van Diepen Erik, Marudkar Mangesh, Hands Oliver, Suribhatla Srinivas, Prettyman Richard, Murray Jonathan, Baillon Sarah, Bhattacharyya Sagnik

机构信息

Senior Clinical Research Fellow, Department of Health Sciences, College of Medicine, Biological Sciences and Psychology, University of Leicester, 22-28 Princess Road West, Leicester LE1 6TP UK.

出版信息

Curr Pharm Des. 2014;20(13):2218-30. doi: 10.2174/13816128113199990434.

Abstract

The endocannabinoid system (ECS) is now recognised as an important modulator of various central nervous system processes. More recently, an increasing body of evidence has accumulated to suggest antioxidant, anti-inflammatory and neuroprotective roles of ECS. In this review we discuss the role and therapeutic potential of ECS in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, Huntington's disease, Tourette's syndrome, brain ischemia and amyotrophic lateral sclerosis (ALS). Elements of the ECS, such as fatty acid amide hydrolase or the cannabinoid receptors are now considered as promising pharmacological targets for some diseases. Although still preliminary, recent reports suggest that modulation of the ECS may constitute a novel approach for the treatment of AD. There are windows of opportunity in conditions caused by acute events such as trauma and ischemia as well in conditions that may involve altered functionality of the target receptors of the ECS, such as in AD. The ECS changes in Parkinson's disease could be compensatory as well as pathogenic of the illness process and needs further understanding and clinical studies are still in the preliminary stage. There is not enough evidence to support use of cannabinoids in treating Huntington's disease, tics and obsessive compulsive behaviour in Tourette's syndrome. Evidence on therapeutic use of cannabinoids in multiple sclerosis and ALS is currently limited. A major challenge for future research is the development of novel compounds with more selectivity for various components of the ECS which could target different neurotoxic pathways and be used in combination therapy.

摘要

内源性大麻素系统(ECS)现已被公认为是各种中枢神经系统过程的重要调节因子。最近,越来越多的证据表明ECS具有抗氧化、抗炎和神经保护作用。在本综述中,我们讨论了ECS在神经退行性疾病中的作用和治疗潜力,如阿尔茨海默病(AD)、帕金森病、多发性硬化症、亨廷顿舞蹈症、妥瑞氏综合征、脑缺血和肌萎缩侧索硬化症(ALS)。ECS的一些成分,如脂肪酸酰胺水解酶或大麻素受体,现在被认为是某些疾病有前景的药理学靶点。尽管仍处于初步阶段,但最近的报告表明,调节ECS可能构成一种治疗AD的新方法。在由创伤和缺血等急性事件引起的疾病中以及在可能涉及ECS靶受体功能改变的疾病中,如AD,都存在机会窗口。帕金森病中ECS的变化可能是对疾病过程的代偿以及致病因素,需要进一步了解,而临床研究仍处于初步阶段。没有足够的证据支持使用大麻素治疗亨廷顿舞蹈症、妥瑞氏综合征中的抽动和强迫行为。目前关于大麻素在多发性硬化症和ALS治疗中的证据有限。未来研究的一个主要挑战是开发对ECS各种成分具有更高选择性的新型化合物,这些化合物可以靶向不同的神经毒性途径并用于联合治疗。

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