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Title

An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease

Authors
Simonin, Yannick
Sonderegger, Peter
Published in Journal of Neuroscience. 2006, vol. 26, no. 41, p. 10614-9
Abstract Various studies suggest that proteolytic activity may be involved in a number of neurodegenerative disorders, including stroke and seizure. In this report, we examined the role of tryptic serine proteases, plasminogen activators (PAs), in the evolution of a neurodegenerative disease. Transgenic mice overexpressing an axonally secreted inhibitor of serine proteases (neuroserpin) were crossed with mice characterized by a "dying-back" motor neuron disease [progressive motor neuronopathy (pmn/pmn)]. Compared with pmn/pmn mice that showed an increase in PA activity, double mutant mice had decreased PA activity in sciatic nerves and spinal cord; their lifespan was increased by 50%, their motor behavior was stabilized, and histological analysis revealed increased numbers of myelinated axons and rescue of motoneuron number and size. This is the first report showing that a class of serine proteases (PAs) may be involved in the pathogenesis of a motor neuron disease and more specifically in axonal degeneration. Inhibiting serine proteases could offer a new strategy for delaying these disorders.
Keywords AnimalsDisease Models, AnimalMiceMice, TransgenicNeurodegenerative Diseases/drug therapy/enzymologyNeuropeptides/biosynthesis/therapeutic useNeuroprotective Agents/metabolism/therapeutic useSerine Endopeptidases/metabolismSerine Proteinase Inhibitors/biosynthesis/therapeutic useSerpins/biosynthesis/therapeutic use
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PMID: 17035547
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SIMONIN, Yannick et al. An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease. In: Journal of Neuroscience, 2006, vol. 26, n° 41, p. 10614-9. https://archive-ouverte.unige.ch/unige:3909

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Deposited on : 2009-10-23

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