tPA promotes ADAMTS-4-induced CSPG degradation, thereby enhancing neuroplasticity following spinal cord injury.
Neurobiol Dis
; 66: 28-42, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24576594
ABSTRACT
Although tissue plasminogen activator (tPA) is known to promote neuronal remodeling in the CNS, no mechanism of how this plastic function takes place has been reported so far. We provide here in vitro and in vivo demonstrations that this serine protease neutralizes inhibitory chondroitin sulfate proteoglycans (CSPGs) by promoting their degradation via the direct activation of endogenous type 4 disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4). Accordingly, in a model of compression-induced spinal cord injury (SCI) in rats, we found that administration of either tPA or its downstream effector ADAMTS-4 restores the tPA-dependent activity lost after the SCI and thereby, reduces content of CSPGs in the spinal cord, a cascade of events leading to an improved axonal regeneration/sprouting and eventually long term functional recovery. This is the first study to reveal a tPA-ADAMTS-4 axis and its function in the CNS. It also raises the prospect of exploiting such cooperation as a therapeutic tool for enhancing recovery after acute CNS injuries.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pró-Colágeno N-Endopeptidase
/
Proteoglicanas de Sulfatos de Condroitina
/
Traumatismos da Medula Espinal
/
Ativador de Plasminogênio Tecidual
/
Fármacos Neuroprotetores
/
Proteínas ADAM
/
Plasticidade Neuronal
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Ano de publicação:
2014
Tipo de documento:
Article