On the structure and functions of gelatinase B/matrix metalloproteinase-9 in neuroinflammation

The blood-brain barrier (BBB) is a specific structure that is composed of two basement membranes (BMs) and that contributes to the control of neuroinflammation. As long as the BBB is intact, extravasated leukocytes may accumulate between two BMs, generating vascular cuffs. Specific matrix metalloproteinases, MMP-2 and MMP-9, have been shown to cleave BBB beta-dystroglycan and to disintegrate thereby the parenchymal BM, resulting in encephalomyelitis. This knowledge has been added to the molecular basis of the REGA model to understand the pathogenesis of multiple sclerosis, and it gives further ground for the use of MMP inhibitors for the treatment of acute neuroinflammation. MMP-9 is associated with central nervous system inflammation and occurs in various forms: monomers and multimers. None of the various neurological and neuropathologic functions of MMP-9 have been associated with either molecular structure or molecular form, and therefore, in-depth structure-function studies are needed before medical intervention with MMP-9-specific inhibitors is initiated.