Urokinase-type plasminogen activator in the ischemic brain

Emory University, Atlanta GA

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Abstract

? DESCRIPTION (provided by applicant): Urokinase-type plasminogen activator (uPA) is a serine proteinase that binds to the urokinase plasminogen activator receptor (uPAR). Although it was initially believed that the main role of uPA-uPAR binding was to catalyze the conversion of plasminogen into plasmin on the cell surface, it was soon discovered that uPAR also activates cell signaling pathways in response to changes in the composition of the extracellular matrix (ECM) leading to tissue remodeling, wound healing, and cell adhesion and migration. uPA and uPAR are expressed in cerebral cortical neurons in the adult brain. In this application we will test the hypothesis that binding of uPA to uPAR in the area surrounding the necrotic core promotes dendritic spine recovery and functional improvement after an ischemic stroke.