Metadatos
Mostrar el registro completo del ítemCompartir este ítem
Targeting Pdzrn3 maintains adult blood-brain barrier and central nervous system homeostasis
Idioma
EN
Article de revue
Este ítem está publicado en
Journal of Cerebral Blood Flow and Metabolism. 2021-10-13p. 271678X211048981
Resumen en inglés
Blood brain barrier (BBB) disruption is a critical component of the pathophysiology of cognitive impairment of vascular etiology (VCI) and associated with Alzheimer's disease (AD). The Wnt pathway plays a crucial role in ...Leer más >
Blood brain barrier (BBB) disruption is a critical component of the pathophysiology of cognitive impairment of vascular etiology (VCI) and associated with Alzheimer's disease (AD). The Wnt pathway plays a crucial role in BBB maintenance, but there is limited data on its role in cognitive pathologies. The E3 ubiquitin ligase PDZRN3 is a regulator of the Wnt pathway. In a murine model of VCI, overexpressing in endothelial cell (EC) exacerbated BBB hyperpermeability and accelerated cognitive decline. We extended these observations, in both VCI and AD models, showing that EC-specific depletion of reinforced the BBB, with a decrease in vascular permeability and a subsequent spare in cognitive decline. We found that in cerebral vessels, Pdzrn3 depletion protects against AD-induced Wnt target gene alterations and enhances endothelial tight junctional proteins. Our results provide evidence that Wnt signaling could be a molecular link regulating BBB integrity and cognitive decline under VCI and AD pathologies.< Leer menos
Palabras clave en inglés
Vascular cognitive impairment
blood brain barrier
vascular permeability
Wnt pathway
endothelial tight junction