PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE BLOOD BRAIN BARRIER: P-glycoprotein and occludin trafficking as therapeutic targets to optimize CNS drug delivery

The blood-brain barrier (BBB) is a physical and metabolic barrier that separates the CNS from the peripheral circulation. CNS drug delivery across the BBB is challenging, primarily due to the physical restriction of paracellular diffusion between the endothelial cells that comprise the microvessels of the BBB and the activity of efflux transporters that quickly expel back into the capillary lumen a wide variety of xenobiotics. Therapeutic manipulation of protein trafficking is emerging as a novel means of modulating protein function, and in this mini-review, the targeting of the trafficking of two key BBB proteins, P-glycoprotein and occludin, is presented as a novel, reversible means of optimizing CNS drug delivery.