Matrix metalloproteinases (MMPs) in health and disease: an overview

摘要: Matrix metalloproteinases (MMPs) are members of an enzyme family that require a zinc ion in their active site for catalytic activity. MMPs critical maintaining tissue allostasis. at neutral pH and can therefore catalyze the normal turnover extracellular matrix (ECM) macromolecules such as interstitial basement membrane collagens, proteoglycans aggrecan, decorin, biglycan, fibromodulin versican well accessory ECM proteins fibronectin. Members MMP include "classical" MMPs, membrane-bound (MT-MMPs) ADAMs (a disintegrin metalloproteinase; adamlysins) ADAMTS metalloproteinase with thrombospondin motif). There more than 20 including collagenases, gelatinases, stromelysins, some elastases aggrecanases. Adamlysins also degrade but importantly, one ADAM member (i.e.ADAM-17) is tumor necrosis factor-alpha (TNF-alpha)-converting (TACE) activates pro-TNF-alpha. Most synthesized inactive latent enzymes. Conversion to generally mediated by activator systems plasminogen or pro-hormone convertase, furin. activity regulated group endogenous proteins, called, inhibitor (TIMPs) bind alternative sites activated MMP. Significant advances have occurred understanding regulation ADAMTSs gene expression. In addition, development inhibitors study structure/function relationships spawned many studies determine effectiveness regulating abnormal connective turnover. null mice carrying specific deletions has provided opportunity explore role diverse conditions diseases skeletal dysplasias, coronary artery heart disease, arthritis, cancer, brain disorders.