A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications.
A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications.
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DOI：
10.1016/j.bbagen.2013.05.011
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发表时间：
2013-10
影响因子：
3
通讯作者：
Mallik, Sanku
中科院分区：
文献类型：
--
作者：
Nyren-Erickson, Erin K.;Jones, Justin M.;Srivastava, D. K.;Mallik, Sanku
解整合素和金属蛋白酶-12（ADAM 12）是酶的大ADAM家族的成员：这些是多功能的，通常是膜结合的锌蛋白酶，已知有40个基因（其中21个出现在人类中）。ADAM 12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和其他生理/病理状况有关。在这篇综述中，我们开始与ADAM家族的酶和蛋白质结构的简要概述。然后，我们讨论了ADAM 12在各种疾病的进展和/或诊断中的作用，我们将以目前已知的天然和合成抑制剂的探索作为结论。ADAM 12有可能成为一个成功的药物靶标，尽管由于ADAM和MMP家族成员之间的结构相似性，很难实现以任何特异性靶向金属蛋白酶结构域。总的来说，需要更多的研究来建立ADAM 12作为不同疾病的高度理想的生物标志物和药物靶标，以及它们的选择性抑制剂作为潜在的治疗剂。考虑到各种疾病，特别是乳腺癌中的ADAM 12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。
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.
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影响因子：
3.8
作者：
Duffy MJ;Mullooly M;O'Donovan N;Sukor S;Crown J;Pierce A;McGowan PM
通讯作者：
McGowan PM
DOI：
10.1158/1541-7786.mcr-11-0100
发表时间：
2011-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Fröhlich C;Nehammer C;Albrechtsen R;Kronqvist P;Kveiborg M;Sehara-Fujisawa A;Mercurio AM;Wewer UM
通讯作者：
Wewer UM
影响因子：
29.4
作者：
Carloni, V;Romanelli, RG;Gentilini, P
通讯作者：
Gentilini, P
影响因子：
4.8
作者：
Gilpin, BJ;Loechel, F;Wewer, UM
通讯作者：
Wewer, UM
影响因子：
3
作者：
Christiansen, Michael;Pihl, Kasper;Larsen, Torben
通讯作者：
Larsen, Torben