Ariel Miller, Yanina. Galboiz, Nitza Lahat, Sarah Shapiro
The Center for Multiple Sclerosis & Brain Research, Department of Neurology,
Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.

MMPs are a family of zinc-dependent proteolytic enzymes that, together with their endogenous tissue inhibitors- TIMPs, are involved in remodeling of the extra cellular matrix (ECM) in a variety of physiological conditions, including embryogenesis and wound healing. Recent studies, however, implicate MMPs to divergent pathological conditions such as: tumor invasion and metastasis, arteriosclerosis, inflammatory and autoimmune diseases. In the pathogenesis of CNS disorders, MMPs seem to play a key role in blood brain barrier (BBB) eruption, brain edema, infiltration of immune cells, myelin degradation and glial-scar formation. In fact, increased activity of MMPs has recently been reported in experimental animal models of demyelinating diseases as well as in multiple sclerosis (MS) patients. MMPs, and in particular increased levels of MMP-2 and -9, were detected in experimental cerebral ischemia as well as in stroke patients. Modulation of MMPs/TIMPs profile seem to be associated also with bacterial and viral meningoencephalitis. Additionally, though results are still controversial, MMPs seem to be involved in the deposition of ?-amyloid protein in Alzheimer's disease.The association of MMPs with CNS disorders has raised considerable interest, as they represent potential bio-markers for disease activity as well as attractive targets for development of novel therapeutic strategies, aimed at inhibiting MMPs' activity. Therefore, understanding the structure and function of these key enzymes may have significant implications for the arresting of evolving brain injury while promoting CNS repair.