Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
Exp Neurol. 2010 Jul;224(1):74-84. doi: 10.1016/j.expneurol.2010.03.025. Epub 2010 Mar 29.
Endocannabinoids (eCBs) include a group of lipid mediators that act as endogenous agonists at cannabinoid (CB(1), CB(2)) and vanilloid (TRPV1) receptors. In the last two decades a number of eCBs-metabolizing enzymes have been discovered that, together with eCBs and congeners, target receptors and proteins responsible for their transport and intracellular trafficking form the so-called "endocannabinoid system" (ECS). Within the central nervous system ECS elements participate in neuroprotection against neuroinflammatory/neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. More recently, a role for eCBs has been documented also in human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120-mediated insults, and in HIV-associated dementia (HAD). The modulation of ECS in the latter disease conditions is the subject of this review, that will also address the molecular mechanisms underlying the neuroprotective effects of eCBs. In particular, the interactions between neurons and glia during neuroinflammation, and the alterations of ECS in these cells upon gp120 insults and HAD will be discussed, along with the potential therapeutic exploitation of ECS-oriented drugs for the treatment of HAD and related disorders.
内源性大麻素（eCBs）包括一组脂质介质，作为大麻素（CB（1）、CB（2））和香草素（TRPV1）受体的内源性激动剂。在过去的二十年中，已经发现了许多 eCBs 代谢酶，它们与 eCBs 和同系物一起，针对负责其运输和细胞内转运的受体和蛋白质，构成了所谓的“内源性大麻素系统”（ECS）。在中枢神经系统中，ECS 元素参与神经保护，以对抗神经炎症/神经退行性疾病，如阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和多发性硬化症。最近，eCBs 在人类免疫缺陷病毒-1（HIV-1）包膜糖蛋白 gp120 介导的损伤以及 HIV 相关痴呆（HAD）中也发挥了作用。本文综述了后者疾病中 ECS 的调节，还探讨了 eCBs 的神经保护作用的分子机制。特别是，在神经炎症期间神经元和神经胶质之间的相互作用，以及 gp120 损伤和 HAD 时这些细胞中 ECS 的改变，将与针对 ECS 的药物治疗 HAD 和相关疾病的潜在治疗利用一起进行讨论。
