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Curr Drug Targets. 2019;20(9):953-959. doi: 10.2174/1389450120666181211144550.

The Plasminogen Activation System Promotes Neurorepair in the Ischemic Brain.

Yepes M1,2,3.

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Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center; Atlanta, GA, United States.
Department of Neurology & Center for Neurodegenerative Disease, Emory University School of Medicine; Atlanta, GA, United States.
Department of Neurology, Veterans Affairs Medical Center; Atlanta, GA, United States.


The plasminogen activation (PA) system was originally thought to exclusively promote the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). However, experimental evidence accumulated over the last 30 years indicates that tPA and uPA are also found in the central nervous system (CNS), where they have a plethora of functions that not always require plasmin generation or fibrin degradation. For example, plasminogen-dependent and - independent effects of tPA and uPA play a central role in the pathophysiological events that underlie one of the leading causes of mortality and disability in the world: cerebral ischemia. Indeed, recent work indicates that while the rapid release of tPA from the presynaptic compartment following the onset of cerebral ischemia protects the synapse from the deleterious effects of the ischemic injury, the secretion of uPA and its binding to its receptor (uPAR) during the recovery phase promotes the repair of synapses that have been lost to the acute ischemic insult. This restorative role of uPA has high translational significance because to this date there is no effective approach to induce neurorepair in the ischemic brain. Here we will discuss recent evidence that bridges the gap between basic research in the field of the PA system and the bedside of ischemic stroke patients, indicating that uPA and uPAR are potential targets for the development of therapeutic strategies to promote neurological recovery among ischemic stroke survivors.


Tissue-type plasminogen activator; cerebral ischemia; neuroprotection; neurorepair; plasmin; urokinase-type plasminogen activator.

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