Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Crit Rev Biochem Mol Biol. 2010 Apr;45(2):146-69. doi: 10.3109/10409231003628015.
This review focuses on the role of ADAM-17 in disease. Since its debut as the tumor necrosis factor converting enzyme (TACE), ADAM-17 has been reported to be an indispensible regulator of almost every cellular event from proliferation to migration. The central role of ADAM-17 in cell regulation is rooted in its diverse array of substrates: cytokines, growth factors, and their receptors as well as adhesion molecules are activated or inactivated by their cleavage with ADAM-17. It is therefore not surprising that ADAM-17 is implicated in numerous human diseases including cancer, heart disease, diabetes, rheumatoid arthritis, kidney fibrosis, Alzheimer's disease, and is a promising target for future treatments. The specific role of ADAM-17 in the pathophysiology of these diseases is very complex and depends on the cellular context. To exploit the therapeutic potential of ADAM-17, it is important to understand how its activity is regulated and how specific organs and cells can be targeted to inactivate or activate the enzyme.
本篇综述聚焦于 ADAM-17 在疾病中的作用。自其作为肿瘤坏死因子转化酶（TACE）首次被报道以来，ADAM-17 已被证实是几乎所有细胞事件（从增殖到迁移）的不可或缺的调节剂。ADAM-17 在细胞调控中的核心作用源于其多样化的底物：细胞因子、生长因子及其受体以及黏附分子通过 ADAM-17 的切割而被激活或失活。因此，ADAM-17 与多种人类疾病（包括癌症、心脏病、糖尿病、类风湿性关节炎、肾纤维化、阿尔茨海默病）有关，这并不奇怪，它是未来治疗的有希望的靶点。ADAM-17 在这些疾病的病理生理学中的具体作用非常复杂，并且取决于细胞环境。为了开发 ADAM-17 的治疗潜力，了解其活性如何被调节以及如何靶向特定的器官和细胞以失活或激活该酶非常重要。
