Endocannabinoid signaling at the periphery: 50 years after THC.

Endocannabinoid signaling at the periphery: 50 years after THC.
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DOI:
10.1016/j.tips.2015.02.008
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发表时间:
2015-05
影响因子:
13.8
通讯作者:
Zimmer, Andreas
Zimmer, Andreas
中科院分区:
医学1区
文献类型:
--
作者:
Maccarrone, Mauro;Bab, Rai;Biro, Tamas;Cabral, Guy A.;Dey, Sudhansu K.;Di Marzo, Vincenzo;Konje, Justin C.;Kunos, George;Mechoulam, Raphael;Pacher, Pal;Sharkey, Keith A.;Zimmer, Andreas

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50年前(1964年),大麻的精神活性成分Δ9-四氢大麻酚(THC)被分离出来。近30年后,THC的内源性对应物,统称为内源性大麻素(eCB),被发现:1992年的N-花生四烯酸乙醇胺(anandamide,AEA)和1995年的2-花生四烯酸甘油(2-AG)。从那时起,大量的研究揭示了eCB对人类健康和疾病的影响,确定了一系列结合,合成和降解它们的蛋白质,并共同形成了eCB系统。eCB控制基本的生物学过程,包括存活和死亡之间的细胞选择,以及祖细胞/干细胞增殖和分化。毫不奇怪,在过去的二十年中,eCB已被公认为人类病理生理学几个方面的关键介质,因此已成为迄今发现的最广泛和最通用的信号分子之一。在这里,这个研究领域的一些先驱回顾了外周器官中关键eCB功能的最新进展。我们的社区努力旨在就外周eCB系统与人类健康和疾病发病机制的相关性建立共识,并强调新出现的挑战和治疗希望。
Fifty years ago (in 1964) the psychoactive ingredient of Cannabis sativa, Δ9-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide, AEA) in 1992, and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize and degrade them, and that altogether form the eCB system. eCBs control basic biological processes, including cell-choice between survival and death, and progenitor/stem cell proliferation and differentiation. Not surprisingly, in the past two decades, eCBs have been recognized as key mediators of several aspects of human pathophysiology, and thus have emerged among the most widespread and versatile signaling molecules ever discovered. Here, some of the pioneers of this research field review the state-of-the-art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral eCB system for human health and disease pathogenesis, as well as to highlight emerging challenges and therapeutic hopes.
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