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Roles of fibrinolytic system components in the nervous system

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Presentation on theme: "Roles of fibrinolytic system components in the nervous system"— Presentation transcript:

1 Roles of fibrinolytic system components in the nervous system
Nobuo Nagai, Osamu Matsuo  Pathophysiology  Volume 17, Issue 2, Pages (April 2010) DOI: /j.pathophys Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions

2 Fig. 1 Protease cascade of the fibrinolytic system and matrix metalloproteinases (MMPs) t-PA and u-PA convert inactive plasminogen to plasmin by limited cleavage, which is inhibited by PAI-1 and -2. Plasmin degrades not only fibrin but also extracellular matrix (ECM) proteins, which is inhibited by α2-antiplasmin. Plasmin can also activate several inactive pro-MMPs to active-MMPs. Active-MMPs degrade various ECM proteins and activate other MMPs. These reactions are inhibited by tissue inhibitors of metalloproteinases (TIMPs), endogenous inhibitors of MMPs. Pathophysiology  , DOI: ( /j.pathophys ) Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions

3 Fig. 2 Receptors of t-PA and signal pathways. t-PA activates intercellular signal pathway through activation of lipoprotein receptor-related protein-1 (LRP-1), N-methyl-d-aspartate receptor (NMDA-R), or annexin A2. There are three signal pathways after LRP-1 activation: NF-κB pathway (1), cAMP/protein kinase A (PKA) pathway (2), and acceleration of the interaction between LRP-1 and NMDA-R via PSD95, a protein of post-synaptic density, and the subsequent ERK1/2 pathway (3). There are two signal pathways related to NMDA-R: t-PA binds to subunit 2 (NR2B) and activation of neuron-type NO synthase (nNOS) through Ca2+/calmodurin pathway (4), and increases Ca2+ influx by NMDA-R ligand through limited cleavage of NMDA-R subunit 1 (NR1B) (5). Annexin A2 is identified as a protein which binds to the internal surface of the cellular membrane. It is not clear how annexin A2 moves to the external surface and how the signal is transferred (6). NPxY; NPxY motif. Pathophysiology  , DOI: ( /j.pathophys ) Copyright © 2009 Elsevier Ireland Ltd Terms and Conditions


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