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An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease
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| Zeitschriftentitel: | The Journal of Neuroscience |
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| Personen und Körperschaften: | , , , , |
| In: | The Journal of Neuroscience, 26, 2006, 41, S. 10614-10619 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>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 (<jats:italic>pmn/pmn</jats:italic>)]. Compared with<jats:italic>pmn/pmn</jats:italic>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.</jats:p> |
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| Umfang: | 10614-10619 |
| ISSN: |
0270-6474
1529-2401 |
| DOI: | 10.1523/jneurosci.3582-06.2006 |