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中枢内源性大麻素受体:预防和治疗神经和精神疾病的潜在药物靶点。

Endocannabinoid Receptors in the CNS: Potential Drug Targets for the Prevention and Treatment of Neurologic and Psychiatric Disorders.

机构信息

Neurochemistry Laboratory, Faculty of Medicine, Universidad Autónoma del Estado de México, Toluca, Mexico.

出版信息

Curr Neuropharmacol. 2020;18(8):769-787. doi: 10.2174/1570159X18666200217140255.

Abstract

The endocannabinoid system participates in the regulation of CNS homeostasis and functions, including neurotransmission, cell signaling, inflammation and oxidative stress, as well as neuronal and glial cell proliferation, differentiation, migration and survival. Endocannabinoids are produced by multiple cell types within the CNS and their main receptors, CB1 and CB2, are expressed in both neurons and glia. Signaling through these receptors is implicated in the modulation of neuronal and glial alterations in neuroinflammatory, neurodegenerative and psychiatric conditions, including Alzheimer's, Parkinson's and Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, stroke, epilepsy, anxiety and depression. The therapeutic potential of endocannabinoid receptors in neurological disease has been hindered by unwelcome side effects of current drugs used to target them; however, due to their extensive expression within the CNS and their involvement in physiological and pathological process in nervous tissue, they are attractive targets for drug development. The present review highlights the potential applications of the endocannabinoid system for the prevention and treatment of neurologic and psychiatric disorders.

摘要

内源性大麻素系统参与中枢神经系统稳态和功能的调节,包括神经传递、细胞信号转导、炎症和氧化应激,以及神经元和神经胶质细胞的增殖、分化、迁移和存活。内源性大麻素由中枢神经系统内的多种细胞类型产生,其主要受体 CB1 和 CB2 在神经元和神经胶质细胞中均有表达。这些受体的信号转导参与了神经炎症、神经退行性和精神疾病中神经元和神经胶质改变的调节,包括阿尔茨海默病、帕金森病和亨廷顿病、多发性硬化症、肌萎缩侧索硬化症、中风、癫痫、焦虑和抑郁。由于目前用于靶向这些受体的药物存在令人不快的副作用,内源性大麻素受体在神经疾病中的治疗潜力受到了阻碍;然而,由于它们在中枢神经系统中的广泛表达及其在神经组织的生理和病理过程中的参与,它们是药物开发的有吸引力的靶点。本综述强调了内源性大麻素系统在预防和治疗神经和精神疾病方面的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3980/7536826/d44112da5daa/CN-18-769_F1.jpg

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