Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid beta-protein precursor abolishes its anti-thrombotic properties in vivo

摘要

Introduction: Kunitz proteinase inhibitor (KPI) domain-containing forms of the amyloid beta-protein precursor (A beta PP) inhibit cerebral thrombosis. KPI domain-lacking forms of A beta PP are abundant in brain. Regions of A beta PP other than the KPI domain may also be involved with regulating cerebral thrombosis. To determine the contribution of the KPI domain to the overall function of A beta PP in regulating cerebral thrombosis we generated a reactive center mutant that was devoid of anti-thrombotic activity and studied its anti-thrombotic function in vitro and in vivo.