An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease.
J Neurosci
; 26(41): 10614-9, 2006 Oct 11.
Article
em En
| MEDLINE
| ID: mdl-17035547
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
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Inibidores de Serina Proteinase
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Serpinas
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Fármacos Neuroprotetores
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Doenças Neurodegenerativas
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Modelos Animais de Doenças
Limite:
Animals
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article