An Inhibitor of Serine Proteases- Neuroserpin- Acts as a Neuroprotective Agent in a Mouse Model of Neurodegenerative Disease-

Authors
Y. Simonin, Y. Charron, P. Sonderegger, J.-D. Vassalli, A. C. Kato.

Lab
University of Geneva, Faculty of Medicine, Departments of Basic Neurosciences and Genetic Medicine and Development, Geneva, Switzerland.

Journal
The Journal of Neurosciences

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.

BIOSEB Instruments Used:
SEDACOM SErial DAta COMmunication Software (SEDACOM)