A disintegrin and metalloproteinase-12 (ADAM12): Function,roles in disease progression,and clinical implications |
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Authors: | Erin K. Nyren-Erickson Justin M. Jones D.K. Srivastava Sanku Mallik |
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Affiliation: | 1. Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108-6050, USA;2. Department of Pharmacy Practice, North Dakota State University, Fargo, ND 58108-6050, USA;3. Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58108-6050, USA |
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Abstract: | BackgroundA 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.ScopeIn 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 conclusionADAM12 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 significanceGiven 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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Keywords: | ADAM12 Disintegrin and metalloproteinase Structure Function Inhibitors |
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