Denis Monard

Our interest in extracellular proteolytic activity in the nervous system stems from our discovery and cloning of protease nexin-1 (PN-1), a potent serine protease inhibitor promoting neurite outgrowth in cultured neuronal cells. Neurite outgrowth occurs by prevention of thrombin activation of aprotease-activated cell surface receptor, which would cause their collapse. Mice lacking or over-expressing PN-1 in neurons are prone to seizure; epileptiform activity is seen in hippocampus slices. Long-term potentiation is enhanced in hippocampal slices from mice with increased PN-1 but reduced in mice lacking PN-1. A study of mice overexpressing PN-1 in postnatal neurons showed that control of extracellular proteolysis is important for neuronal function in vivo. These animals allow study of early events in certain motor neuron diseases. In PN-1 knockout mice, we identified phosphatidylethanolamine-binding protein as a novel serine protease inhibitor not exclusive to the nervous system.
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