Regulation of ABC Transporters at the Blood-Brain Barrier: New Targets for CNS Therapy

Regulation of BBB ABC transporters by inflammatory mediators and oxidative stress. (A and B) Time-dependent regulation of P-glycoprotein through a signaling pathway that involves the pro-inflammatory mediator tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNF-R1), endothelin-converting enzyme (ECE), endothelin-1 (ET-1), endothelin A and B receptors (ETA/B), nitric oxide synthase (NOS), protein kinase C (PKC), and nuclear factor-κB (NF-κB). (C) Regulation of P-glycoprotein through a signaling pathway that involves the reactive oxygen species hydrogen peroxide (H₂O₂), extracellular signal-regulated kinase 1/2 (ERK1/2), stress-activated protein kinase (SAPK), protein kinase B (Akt), and protein kinase C (PKC). (D) Regulation of P-glycoprotein through a signaling pathway that is triggered by DEP (diesel exhaust particles) and involves NADPH oxidase (PHOX), reactive oxygen species (ROS), TNF-α-converting enzyme (TACE), TNF-α, TNF-R1, c-Jun N-terminal kinase (JNK), and activator protein-1 (AP-1).