Instituto de Biomedicina de Valencia, CSIC, Jaime Roig 11, 46010 Valencia, Spain.
Toxicon. 2013 Feb;62:40-9. doi: 10.1016/j.toxicon.2012.09.005. Epub 2012 Sep 23.
Disintegrins, a family of polypeptides released in the venoms of viperid snakes (vipers and rattlesnakes) by the proteolytic processing of multidomain metalloproteinases, selectively block the function of β(1) and β(3) integrin receptors. Few of the proteins isolated and characterized from snake venoms have proven to be more structural and functional versatile than the disintegrins. Not surprisingly, 25 years after their discovery, our knowledge on the evolutionary history and the molecular determinants modulating the integrin inhibitory activity of disintegrins still remain fragmentary. This paper highlights some seminal contributions, including personal accounts of pioneer authors, related to basic and applied research on disintegrins. Investigators have evaluated disintegrin applications in therapies for a number of pathologies in which integrin receptors play relevant roles, particularly myocardial infarction and inappropriate tumor angiogenesis. Completing the continuing story of the disintegrin family by applying novel research approaches may hold the key to learn how to use deadly toxins as therapeutic agents.
整合素降解酶，一类多结构域金属蛋白酶在蝰蛇（包括响尾蛇和蝮蛇）毒液中切割释放的多肽，能选择性地阻断β(1)和β(3)整合素受体的功能。从蛇毒中分离和鉴定的蛋白中，几乎没有比整合素降解酶具有更多结构和功能多样性的。毫不奇怪，在发现后的 25 年里，我们对整合素降解酶进化历史和调节其整合素抑制活性的分子决定因素的了解仍然很零碎。本文重点介绍了一些开创性的贡献，包括主要作者的个人叙述，这些贡献与整合素降解酶的基础和应用研究有关。研究人员已经评估了整合素降解酶在治疗多种与整合素受体发挥重要作用的疾病中的应用，特别是心肌梗死和肿瘤血管生成异常。通过应用新的研究方法来补充整合素降解酶家族的故事，可能是了解如何将致命毒素用作治疗剂的关键。
