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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 |
|---|---|
| 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: |
| author_facet |
Simonin, Yannick Charron, Yves Sonderegger, Peter Vassalli, Jean-Dominique Kato, Ann C. Simonin, Yannick Charron, Yves Sonderegger, Peter Vassalli, Jean-Dominique Kato, Ann C. |
|---|---|
| author |
Simonin, Yannick Charron, Yves Sonderegger, Peter Vassalli, Jean-Dominique Kato, Ann C. |
| spellingShingle |
Simonin, Yannick Charron, Yves Sonderegger, Peter Vassalli, Jean-Dominique Kato, Ann C. The Journal of Neuroscience An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease General Neuroscience |
| author_sort |
simonin, yannick |
| spelling |
Simonin, Yannick Charron, Yves Sonderegger, Peter Vassalli, Jean-Dominique Kato, Ann C. 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.3582-06.2006 <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> An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease The Journal of Neuroscience |
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| title |
An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_unstemmed |
An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_full |
An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_fullStr |
An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_full_unstemmed |
An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_short |
An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_sort |
an inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.3582-06.2006 |
| publishDate |
2006 |
| physical |
10614-10619 |
| description |
<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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| author | Simonin, Yannick, Charron, Yves, Sonderegger, Peter, Vassalli, Jean-Dominique, Kato, Ann C. |
| author_facet | Simonin, Yannick, Charron, Yves, Sonderegger, Peter, Vassalli, Jean-Dominique, Kato, Ann C., Simonin, Yannick, Charron, Yves, Sonderegger, Peter, Vassalli, Jean-Dominique, Kato, Ann C. |
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| description | <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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| spelling | Simonin, Yannick Charron, Yves Sonderegger, Peter Vassalli, Jean-Dominique Kato, Ann C. 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.3582-06.2006 <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> An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease The Journal of Neuroscience |
| spellingShingle | Simonin, Yannick, Charron, Yves, Sonderegger, Peter, Vassalli, Jean-Dominique, Kato, Ann C., The Journal of Neuroscience, An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease, General Neuroscience |
| title | An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_full | An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_fullStr | An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_full_unstemmed | An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_short | An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| title_sort | an inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease |
| title_unstemmed | An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.3582-06.2006 |