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The Dual Role of Serpins and Tissue-Type Plasminogen Activator During Stroke

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The Serpin Family

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Abstract

Serpins are well-known inhibitors of plasminogen activators, key components of fibrinolysis. Within the last decades, tissue-type plasminogen activator (tPA) became more than a fibrinolytic agent and has been demonstrated to be a neuromodulator with physiological and pathological roles within the brain. Indeed, tPA is involved in brain plasticity, learning and memory and development. But in a stroke context, tPA contributes to the increase of intraneuronal calcium, by interacting with the GluN1 subunit of the NMDA receptor, leading to an increase in excitotoxicity. It also promotes blood-brain barrier leakage and inflammation, but in certain conditions tPA can also exert beneficial effects in stroke.

These complex effects of the protease can be inhibited by several serpins, such as neuroserpin, plasminogen activator inhibitor (PAI)-1 and protease nexin (PN)-1. In this chapter, we will focus on the differential effects of the plasminogen activator tPA and make an overview of the literature about serpins’ effects on the cerebral roles of tPA.

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  1. INSERM, INSERM U919, University Caen Basse Normandie, Serine Proteases and Pathophysiology of the Neurovascular Unit, Public Interest Group CYCERON, Boulevard Becquerel, 14074, Caen, France

    Benoit D. Roussel, Morgane Louessard, Sara Martinez de Lizarrondo & Denis Vivien

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  1. Benoit D. Roussel
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Correspondence to Benoit D. Roussel .

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  1. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Margarethe Geiger

  2. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

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  3. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria

    Margareta Furtmüller

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Roussel, B.D., Louessard, M., de Lizarrondo, S.M., Vivien, D. (2015). The Dual Role of Serpins and Tissue-Type Plasminogen Activator During Stroke. In: Geiger, M., Wahlmüller, F., Furtmüller, M. (eds) The Serpin Family. Springer, Cham. https://doi.org/10.1007/978-3-319-22711-5_16

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