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Scientific article
English

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

Published inThe Journal of neuroscience, vol. 26, no. 41, p. 10614-10619
Publication date2006
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
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: The Journal of neuroscience, 2006, vol. 26, n° 41, p. 10614–10619. doi: 10.1523/JNEUROSCI.3582-06.2006
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Article (Accepted version)
accessLevelRestricted
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ISSN of the journal0270-6474
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