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Physiology and Pathophysiology of the Blood-Brain Barrier: P-Glycoprotein and Occludin Trafficking as Therapeutic Targets to Optimize Central Nervous System Drug Delivery.


J Investig Med. 2012 Nov 7;


Authors: McCaffrey G, Davis TP


Abstract

ABSTRACT: The blood-brain barrier (BBB) is a physical and metabolic barrier that separates the central nervous system from the peripheral circulation. Central nervous system drug delivery across the BBB is challenging, primarily because of 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 minireview, the targeting of the trafficking of 2 key BBB proteins, P-glycoprotein and occludin, is presented as a novel, reversible means of optimizing central nervous system drug delivery.

PMID: 23138008 [PubMed - as supplied by publisher]