Journal
JOURNAL OF INVESTIGATIVE MEDICINE
Volume 60, Issue 8, Pages 1131-1140Publisher
BMJ PUBLISHING GROUP
DOI: 10.2310/JIM.0b013e318276de79
Keywords
blood-brain barrier; CNS drug delivery; protein trafficking; protein-protein interaction; oxidative stress; peripheral inflammatory pain; P-glycoprotein; occludin
Funding
- National Institutes of Health [R01-NS 39592, R01-NS42652, R01-DA12684, CA 09820-0251]
- National Center for Research Resources [R13 RR023236]
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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.
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