Nyren-Erickson Erin K, Jones Justin M, Srivastava D K, Mallik Sanku
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108-6050, USA.
Biochim Biophys Acta. 2013 Oct;1830(10):4445-55. doi: 10.1016/j.bbagen.2013.05.011. Epub 2013 May 13.
A disintegrin and metalloproteinase-12 (ADAM12) is a member of the greater ADAM family of enzymes: these are multifunctional, generally membrane-bound, zinc proteases for which there are forty genes known (21 of these appearing in humans). ADAM12 has been implicated in the pathogenesis of various cancers, liver fibrogenesis, hypertension, and asthma, and its elevation or decrease in human serum has been linked to these and other physiological/pathological conditions.
In this review, we begin with a brief overview of the ADAM family of enzymes and protein structure. We then discuss the role of ADAM12 in the progression and/or diagnosis of various disease conditions, and we will conclude with an exploration of currently known natural and synthetic inhibitors.
ADAM12 has potential to emerge as a successful drug target, although targeting the metalloproteinase domain with any specificity will be difficult to achieve due to structural similarity between the members of the ADAM and MMP family of enzymes. Overall, more research is required to establish ADAM12 being as a highly desirable biomarker and drug target of different diseases, and their selective inhibitors as potential therapeutic agents.
Given the appearance of elevated levels of ADAM12 in various diseases, particularly breast cancer, our understanding of this enzyme both as a biomarker and a potential drug target could help make significant inroads into both early diagnosis and treatment of disease.
解整合素金属蛋白酶12（ADAM12）是更大的ADAM酶家族的成员之一：这些酶具有多种功能，通常与膜结合，属于锌蛋白酶，已知有40个基因（其中21个出现在人类中）。ADAM12与多种癌症、肝纤维化、高血压和哮喘的发病机制有关，其在人血清中的升高或降低与这些及其他生理/病理状况相关。
在本综述中，我们首先简要概述ADAM酶家族及其蛋白质结构。然后我们讨论ADAM12在各种疾病进展和/或诊断中的作用，最后将探讨目前已知的天然和合成抑制剂。
ADAM12有潜力成为一个成功的药物靶点，尽管由于ADAM和MMP酶家族成员之间的结构相似性，很难以任何特异性靶向金属蛋白酶结构域。总体而言，需要更多研究来确定ADAM12作为不同疾病的理想生物标志物和药物靶点，以及其选择性抑制剂作为潜在治疗剂。
鉴于ADAM12在各种疾病，特别是乳腺癌中水平升高，我们对这种酶作为生物标志物和潜在药物靶点的理解可能有助于在疾病的早期诊断和治疗方面取得重大进展。
