Denis Monard

Denis Monard
Modulation of neural functions by extracellular serine proteases and their inhibitors
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.
Meins M, Piosik P, Schaeren-Wiemers N, Franzoni S, Troncoso E, Kiss JZ, Brösamle C, Schwab ME, Molnar Z, Monard D (2001) Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor Nexin-1 in postmitotic neurons
J Neurosci 21:8830-8841Drapkin PT, Monard D, Silverman A-J (2002) The role of serine proteases and serine protease inhibitors in the migration of Gonadotropin-Releasing Hormone neurons
BMC Dev Biol 2:1-11Altrogge LM, Monard D (2000) An assay for high-sensitivity detection of thrombin activity and determination of proteases activating or inactivating protease-activated receptors
Ann Biochem 277:33-45Hengst U, Albrecht H, Hess D, Monard D (2001) The phosphatidylethanolamine-binding protein is the prototype of a novel family of serine protease inhibitors
J Biol Chem 276:535-540Sinnreich M, Meins M, Niclou P, Suidan HS, Monard D (2003) Prothrombin overexpressed in postnatal neurons requires blood factors for activation in the mouse brain
SubmittedKvajo M, Albrecht H, Meins M, Hengst U, Troncoso E, Kiss J, Monard D (2003) Experience-dependent regulation of brain proteolytic activity is crucial for the proper in vivo function of the NMDA recept
Submitted to NeuronMurer V, Spetz JF, Hengst U, Altrogge LM, de Agostini A, Monard D (2001) Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1
Proc Natl Acad Sci USA 98:3029-3033