Biology of metalloproteinases

Matrix metalloproteinases (MMPs) occupy a central role in embryogenesis and in normal physiological conditions, such as proliferation, cell motility, remodeling, wound healing, angiogenesis, and key reproductive events. MMPs form a multigenic family of proteolytic, zinc-dependent enzymes, with 26 members described until present, displaying multidomain structures and substrate specificities. MMPs are involved in both the turnover and degradation of extracellular matrix (ECM) proteins and in the processing, activation, or deactivation of a variety of soluble factors. They are regulated at the level of transcription, activation of the precursor zymogens, and inhibition mainly by tissue inhibitors of metalloproteinases (TIMPs). Any loss in activity control may result in various diseases. This review provides an update of biological functions of MMPs, facilitating the understanding of the complex pathogenic mechanisms of medical conditions characterized by imbalance between MMP and TIMP expression. The design of potent specific inhibitors for MMPs represents a scientific challenge for the development of new therapies.