No conflicts of interest were declared.
Adamalysins in biology and disease†
Article first published online: 22 JUN 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 219, Issue 3, pages 277–286, November 2009
How to Cite
van Goor, H., Melenhorst, W. B., Turner, A. J. and Holgate, S. T. (2009), Adamalysins in biology and disease. J. Pathol., 219: 277–286. doi: 10.1002/path.2594
- Issue published online: 9 OCT 2009
- Article first published online: 22 JUN 2009
- Accepted manuscript online: 22 JUN 2009 12:00AM EST
- Manuscript Accepted: 17 JUN 2009
- Manuscript Revised: 11 JUN 2009
- Manuscript Received: 19 MAR 2009
- Dutch Kidney Foundation
- UK MRC
ADAMs (adisintegrin and metalloprotease) are membrane-bound enzymes, capable of shedding a multitude of proteins from the surface of the cell. They are therefore considered crucial modulators of physiological and pathophysiological processes. The structure and function of ADAMs is related to those of a family of snake venom metalloproteases which also possess a potential adhesion domain as well as a potential protease domain. Mammalian ADAMs are involved in various biological and disease-related processes, such as cell–cell fusion, adhesion and intracellular signalling. Functional involvement has been described in sperm–egg binding and fusion, trophoblast invasion and matrix degradation during pregnancy, angiogenesis and neovascularization. Clinically, ADAMs are implicated in pathological processes, including cancer, inflammation, neurodegeneration and fibrosis, through shedding of the apoptosis-inducing FAS ligand, cytokines and growth factors. A second group of proteins within the ADAM family has recently been discovered. These contain several thrombospondin-like repeats in their C-terminal regions, in the absence of the transmembrane domain known to be present in ADAMs. These proteins were called the ADAMTS (ADAM with thrombospondin domains) family. The relevance of ADAMTS enzymes has become evident in patients with a deficiency in ADAMTS-13, a von Willebrand factor cleaving protease. These patients develop thrombotic thrombocytopenic purpura, a devastating thrombotic disorder caused by widespread microvascular thrombi composed of platelets and von Willebrand factor (VWF). Here we focus on the genetic, developmental, functional and disease-related aspects of ADAMs and ADAMTS. Finally we discuss the perspectives of the therapeutical potential of ADAMs in disease. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.