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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
Charron, Yves
Sonderegger, Peter
Vassalli, Jean-Dominique
Kato, Ann Catherine
Published in The 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 Animals — Disease Models, Animal — Mice — Mice, Transgenic — Neurodegenerative Diseases/drug therapy/enzymology — Neuropeptides/biosynthesis/therapeutic use — Neuroprotective Agents/metabolism/therapeutic use — Serine Endopeptidases/metabolism — Serine Proteinase Inhibitors/biosynthesis/therapeutic use — Serpins/biosynthesis/therapeutic use
Identifiers
PMID: 17035547
Full text
Article (Accepted version) (552 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www.jneurosci.org/cgi/content/full/26/41/10614
Structures
Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales
Citation
(ISO format) 		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. doi: 10.1523/JNEUROSCI.3582-06.2006 https://archive-ouverte.unige.ch/unige:3909

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Deposited on : 2009-10-23

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