MATRIX METALLOPROTEINASES, TUMOR-NECROSIS-FACTOR AND MULTIPLE-SCLEROSIS - AN OVERVIEW

The matrix metalloproteinases (MMPs) are a family of at least 14 zinc- dependent enzymes which are known to degrade the protein components of extracellular matrix. In adddition, MMPs and related enzymes can also process a number of cell surface cytokines, receptors, and other solu ble proteins. In particular we have shown that the release of the pro- inflammatory cytokine, tumor necrosis factor-alpha, from its membrane- bound precursor is an MMP-dependent process. MMPs are expressed by the inflammatory cells which are associated with CNS lesions in animal mo dels of multiple sclerosis (MS) and in tissue from patients with the d isease. MMP expression will contribute to the tissue destruction and i nflammation in MS. Drugs which inhibit MMP activity are effective in a nimal models of MS and may prove to be useful therapies in the clinic.