Activated protein C promotes neuroprotection: mechanisms and translation to the clinic. Issue 141 (May 2016)

• Record Type: Journal Article
• Authors: Griffin, John H.; Fernández, José A.; Lyden, Patrick D.; Zlokovic, Berislav V.
• Is Part Of: Thrombosis research. Issue 141(2016)Supplement 2
• Page Start: S62
• Page End: S64
• Publication Date: 2016-05
• Subjects: activated protein C (APC) -- stroke -- neuroprotection -- neurogenesis -- traumatic brain injury; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/S0049-3848(16)30368-1
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Activated protein C (APC) is a plasma serine protease that is capable of antithrombotic, anti-inflammatory, anti-apoptotic, and cell-signaling activities. Animal injury studies show that recombinant APC and some of its mutants are remarkably therapeutic for a wide range of injuries. In particular, for neurologic injuries, APC reduces damage caused by ischemia/reperfusion in the brain, by acute brain trauma, and by chronic neurodegenerative conditions. For these neuroprotective effects, APC requires endothelial cell protein C receptor. APC activates cell signaling networks with alterations in gene expression profiles by activating protease activated receptors 1 and 3. To minimize APC-induced bleeding risk, APC variants were engineered to lack > 90% anticoagulant activity but retain normal cell signaling. The neuroprotective APC mutant, 3K3A-APC which has Lys191–193 mutated to Ala191–193, is very neuroprotective and it is currently in clinical trials for ischemic stroke.