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Article Dans Une Revue Journal of Cerebral Blood Flow and Metabolism Année : 2021

Targeting Pdzrn3 maintains adult blood-brain barrier and central nervous system homeostasis.

Résumé

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.
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Dates et versions

hal-03555717 , version 1 (11-04-2022)

Identifiants

Citer

Florian Gueniot, Sebastien Rubin, Pauline Bougaran, Alice Abelanet, Jean Luc Morel, et al.. Targeting Pdzrn3 maintains adult blood-brain barrier and central nervous system homeostasis.. Journal of Cerebral Blood Flow and Metabolism, 2021, pp.271678X211048981. ⟨10.1177/0271678X211048981⟩. ⟨hal-03555717⟩
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