Adamalysins in biology and disease

Harry van Goor*, Wynand B. W. H. Melenhorst, Anthony J. Turner, Stephen T. Holgate

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

61 Citaten (Scopus)


ADAMs (a disintegrin 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.

Originele taal-2English
Pagina's (van-tot)277-286
Aantal pagina's10
Nummer van het tijdschrift3
StatusPublished - nov-2009

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