PT  - JOURNAL ARTICLE
AU  - Yannick Simonin
AU  - Yves Charron
AU  - Peter Sonderegger
AU  - Jean-Dominique Vassalli
AU  - Ann C. Kato
TI  - An Inhibitor of Serine Proteases, Neuroserpin, Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease
AID  - 10.1523/JNEUROSCI.3582-06.2006
DP  - 2006 Oct 11
TA  - The Journal of Neuroscience
PG  - 10614--10619
VI  - 26
IP  - 41
4099  - http://www.jneurosci.org/content/26/41/10614.short
4100  - http://www.jneurosci.org/content/26/41/10614.full
SO  - J. Neurosci.2006 Oct 11; 26
AB  - 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.