An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease
| Autor: | Ann Catherine Kato, Peter Sonderegger, Yannick Simonin, Yves Charron, Jean-Dominique Vassalli |
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| Přispěvatelé: | University of Zurich, Kato, A C |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Genetically modified mouse
Proteases Serine Proteinase Inhibitors Neuroprotective Agents/metabolism/therapeutic use Mice Transgenic Biology Neuroprotection Serine Mice Serine Endopeptidases/metabolism Neuroserpin medicine 10019 Department of Biochemistry Animals Serpins/biosynthesis/therapeutic use ddc:576.5 Axon Neurodegenerative Diseases/drug therapy/enzymology Serpins General Neuroscience Neuropeptides Serine Endopeptidases 2800 General Neuroscience Neurodegenerative Diseases Motor neuron Cell biology ddc:616.8 Serine Proteinase Inhibitors/biosynthesis/therapeutic use Disease Models Animal medicine.anatomical_structure Neuroprotective Agents Biochemistry nervous system 570 Life sciences biology Neuropeptides/biosynthesis/therapeutic use Brief Communications Plasminogen activator |
| Zdroj: | Journal of Neuroscience, Vol. 26, No 41 (2006) pp. 10614-9 |
| ISSN: | 0270-6474 |
| Popis: | 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 withpmn/pmnmice 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. |
| Databáze: | OpenAIRE |
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