| First Author | Simonin Y | Year | 2006 |
| Journal | J Neurosci | Volume | 26 |
| Issue | 41 | Pages | 10614-9 |
| PubMed ID | 17035547 | Mgi Jnum | J:113248 |
| Mgi Id | MGI:3664847 | Doi | 10.1523/JNEUROSCI.3582-06.2006 |
| Citation | Simonin Y, et al. (2006) An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease. J Neurosci 26(41):10614-9 |
| abstractText | 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. |
