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A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications

hxt_hz 添加于 2013-9-28 22:03 | 1452 次阅读 | 0 个评论

作者
Nyren-Erickson EK, Jones JM, Srivastava DK, Mallik S
摘要
BACKGROUND: 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. SCOPE: 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. MAJOR CONCLUSION: 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. GENERAL SIGNIFICANCE: 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.
详细资料
- 关键词: Adam12; Disintegrin and metalloproteinase; Function; Inhibitors; Structure
- 文献种类:期刊
- 期刊名称: Biochimica et Biophysica Acta
- 期刊缩写: Biochim Biophys Acta
- 期卷页: 2013年第1830卷第10期 4445-4455页
- 地址: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108-6050, USA
- ISBN: 0006-3002
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