Rab7a is required to degrade select blood-brain barrier junctional proteins after ischemic stroke.

ABSTRACT: Adherens (AJ) and tight junction (TJ) integrity is critical for blood-brain barrier (BBB) function in the healthy brain. Junction disassembly due to degradation of AJ and TJ proteins leads to acute BBB dysfunction after ischemic stroke, but the mechanisms are not fully understood. Here, we show that endothelial cell deletion of Rab7a, a small GTPase crucial for protein degradation through the endolysosomal system, reduces acute BBB dysfunction and improves neuronal health in mice after ischemic stroke by preventing degradation of select junctional proteins and preserving TJ structural morphology. Two pro-inflammatory cytokines, TNFα and IL1β, that trigger barrier disruption in brain endothelial cells (BECs) in vitro and are upregulated in stroke, contribute to Rab7a activation. Sile

SUBMITTER: Cottarelli A 

PROVIDER: S-EPMC10491261 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature