金属蛋白酶是一组在细胞外基质重塑及其分子信号传导方面具有重要作用的蛋白酶。在这些金属蛋白酶中，ADAMs（解离素和金属蛋白酶）和ADAM-TSs（带有血小板凝血素结构域的ADAMs）已成为高效介导各种信号分子蛋白水解加工的贡献者。ADAMs是跨膜金属酶，能促进膜锚定蛋白，细胞因子，生长因子，配体及其受体的细胞外区段脱离，并调节它们的生物功能。ADAM-TSs是分泌性和可溶性的细胞外蛋白酶，介导非纤维细胞外基质蛋白的裂解。ADAMs和ADAM-TSs共同具有前序域，金属蛋白酶，解离素和半胱氨酸富含结构域，但ADAM-TSs的特征性血小板凝血素可以代替跨膜区。大多数ADAMs和ADAM-TSs都通过前序域的剪切而被激活，剪切点位于它们的N-末端，从而将它们定向到各种信号通路。在本文中，我们不仅讨论了ADAMs和ADAM-TSs的结构和调节，还阐述了这些金属蛋白酶在心血管疾病，结直肠癌，自身炎症性疾病（脓毒症/类风湿性关节炎），阿尔茨海默病，增生性视网膜病和传染性疾病等各种人类病理生理学条件中的重要性。因此，根据ADAMs和ADAM-TSs在各种人类病理生理学中的不断涌现的作用，如本综述所总结的，这些金属蛋白酶可以被视为重要的治疗靶点和诊断生物标志物。©2021年。作者（们）根据对Springer Nature Switzerland AG的专属许可。

Metalloproteinases are a group of proteinases that plays a substantial role in extracellular matrix remodeling and its molecular signaling. Among these metalloproteinases, ADAMs (a disintegrin and metalloproteinases) and ADAM-TSs (ADAMs with thrombospondin domains) have emerged as highly efficient contributors mediating proteolytic processing of various signaling molecules. ADAMs are transmembrane metalloenzymes that facilitate the extracellular domain shedding of membrane-anchored proteins, cytokines, growth factors, ligands, and their receptors and therefore modulate their biological functions. ADAM-TSs are secretory, and soluble extracellular proteinases that mediate the cleavage of non-fibrillar extracellular matrix proteins. ADAMs and ADAM-TSs possess pro-domain, metalloproteinase, disintegrin, and cysteine-rich domains in common, but ADAM-TSs have characteristic thrombospondin motifs instead of the transmembrane domain. Most ADAMs and ADAM-TSs are activated by cleavage of pro-domain via pro-protein convertases at their N-terminus, hence directing them to various signaling pathways. In this article, we are discussing not only the structure and regulation of ADAMs and ADAM-TSs, but also the importance of these metalloproteinases in various human pathophysiological conditions like cardiovascular diseases, colorectal cancer, autoinflammatory diseases (sepsis/rheumatoid arthritis), Alzheimer's disease, proliferative retinopathies, and infectious diseases. Therefore, based on the emerging role of ADAMs and ADAM-TSs in various human pathologies, as summarized in this review, these metalloproteases can be considered as critical therapeutic targets and diagnostic biomarkers.© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.