Death Receptors and Their Ligands in Inflammatory Disease and Cancer
Death Receptors and Their Ligands in Inflammatory Disease and Cancer
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DOI：
10.1101/cshperspect.a036384
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发表时间：
2020-09-01
影响因子：
7.2
通讯作者：
Walczak, Henning
中科院分区：
文献类型：
--
作者：
Annibaldi, Alessandro;Walczak, Henning
在与其同源配体结合时，死亡受体可以启动级联事件，这可以导致两种不同的结果：基因表达和细胞死亡。在过去的50年里，三种不同的死亡受体-配体系统，肿瘤坏死因子（TNF）-TNF受体1（TNFR 1），CD 95 L-CD 95和TNF相关凋亡诱导配体（TRAIL）-TRAIL-R1/2系统的研究引起了几代科学家的关注。正如科学界经常发生的那样，这种科学之旅绝不是一条通往成功的直线，该领域的发现往往是偶然发现的，让科学家们大吃一惊。然而，正如路易斯·巴斯德指出的那样，运气更喜欢有准备的头脑。因此，迄今为止该领域最具影响力的发现，即TNF抑制作为几种炎症和自身免疫性疾病的有效治疗的事实，是这样的，这并不奇怪。幸运的是，做出这一发现的科学家们已经做好了准备，最重要的是，他们决心利用他们的发现来获得治疗益处。今天对这些死亡受体-配体系统的研究已经发现了由各种这些系统诱导的细胞死亡与炎症之间的因果关系。在这篇综述中，我们解释了为什么我们预测这一发现的治疗利用可能会深刻影响未来的治疗炎症性疾病和癌症。
On binding to their cognate ligands, death receptors can initiate a cascade of events that can result in two distinct outcomes: gene expression and cell death. The study of three different death receptor-ligand systems, the tumor necrosis factor (TNF)-TNF receptor 1 (TNFR1), the CD95L-CD95, and the TNF-related apoptosis-inducing ligand (TRAIL)-TRAIL-R1/2 system, has drawn the attention of generations of scientists over the past 50 years. This scientific journey, as often happens in science, has been anything but a straight line to success and discoveries in this field were often made by serendipity, catching the scientists by surprise. However, as Louis Pasteur pointed out, luck prefers the prepared mind. It is therefore not surprising that the most impactful discovery of the field to date, the fact that TNF inhibition serves as an effective treatment for several inflammatory and autoimmune diseases, has been like this. Luckily, the scientists who made this discovery were prepared and, most importantly, determined to harness their discovery for therapeutic benefit. Today's research on these death receptor-ligand systems has led to the discovery of a causal link between cell death induced by a variety of these systems and inflammation. In this review, we explain why we predict that therapeutic exploitation of this discovery may profoundly impact the future treatment inflammatory disease and cancer.