Mmp-9 inhibitors in the brain: can old bullets shoot new targets?

Matrix metalloproteinases (MMPs) are either secreted or membrane-bound proteases, capable to degrade extracellular matrix (ECM) proteins as well as a large number of non-ECM proteins, such as growth factors, cytokines, chemokines, cell surface receptors, serine proteinase inhibitors and other MMPs. MMPs play major physiological roles in reproduction, growth, development, angiogenesis, immune response, wound healing and brain physiology. MMPs, and especially MMP-2 and -9 were considered to be targets for drug development (especially in oncology) and over fifty MMP inhibitors have been pursued in clinical trials that, however, failed mainly for the reason of insufficient knowledge about complexity of the biology. Recent studies implicating MMP-9 in aberrant synaptic plasticity underlying neuropsychiatric disorders, as well as in aggravating detrimental effects of the brain stroke, appear to offer a new hope for application of MMP inhibitors in treatment of those conditions.