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lüll ADAM-17: the enzyme that does it all Gooz MCrit Rev Biochem Mol Biol 2010[Apr]; 45 (2): 146-69This 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.|ADAM Proteins/antagonists & inhibitors/chemistry/*physiology[MESH]|ADAM17 Protein[MESH]|Animals[MESH]|Disease[MESH]|Enzyme Activation[MESH]|Enzyme Inhibitors/pharmacology[MESH]|Humans[MESH]|Inflammation/drug therapy/enzymology[MESH]|Substrate Specificity[MESH]|Tumor Necrosis Factor-alpha/metabolism[MESH] |