Mmp-9, a potential target for cerebral ischemic treatment

Abstract

Matrix metalloproteinase-9 (MMP-9) which is a member of matrix metalloproteinases family that normally remodel the extracellular matrix, has been shown to play an important role in both animal models of cerebral ischemia and human stroke. The expression of MMP-9 is elevated after cerebral ischemia which is involved in accelerating matrix degradation, disrupting the blood-brain barrier, increasing the infarct size and relating to hemorrhagic transformation. Recently, many drugs, such as tetracycline derivatives, cyclooxygenase inhibitors, ACEI inhibitors and AT1 receptor blockers, etc., have been found to attenuate the elevated expression levels of MMP-9 after ischemia and to reduce the damage of cerebral ischemic. This article reviews the physiological features of MMP-9 and its important role in the genesis, propagation, and therapeutics of cerebral ischemic diseases.

Keywords: Matrix metalloproteinase-9 (MMP-9); cerebral ischemia; regulation; therapeutical target..

Fig. (1)

(A) The domain structure of MMP-9. S – signal peptide; C – catalytic domain; F – fibronectin type II domain; L – linkage domain; HP – hemopexin like domain. (B) Schematic drawing to show the process of MMP-9 expression and regulation. Akt – Protein kinase B (PKB); ECM – extracellular matrix; MMP – matrix metalloproteinase; PI3K – phosphatidylinositol 3-kinase; Pol II – RNA polymerase II; TIMP – tissue inhibitor of metalloproteinase; uPA – urokinase type plasminogen activator; tPA – tissue type plasminogen activator; ERK – extracellular signal activated protein kinase; MEK – mitogen activated ERK activating kinase; NO – nitric oxide. Boxes in nucleus indicate the following cis elements: AP-1 – activator protein-1; PEA3 – polyoma enhancer A binding protein-3; GC – Sp-1 binding site; NF-κB – nuclear factor κB; TATA – TATA box.