Fig. 3

Multifaceted roles of TGF-β signaling in BBB integrity. In the canonical pathway, TGF-β binding to the TGFBR1 and TGFBR2 receptors leads to the phosphorylation and activation of TGFBR1. Activated TGFBR1 then phosphorylates SMAD2 and SMAD3. These phosphorylated SMADs form a complex with SMAD4 and translocate to the nucleus, where they regulate gene expression. Activation of TGF-β signaling can regulate multiple aspects of BBB Integrity: impacting transcytosis, expression of junction proteins, interactions between endothelial cells and pericytes, and endothelial-to-mesenchymal transition (EndoMT). The effects of TGF-β signaling activation are highly context-dependent. Dysregulated TGF-β signaling after TBI and in AD impairs BBB integrity. Created with BioRender.com