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Physiology and Pathophysiology of the Blood-Brain Barrier
  1. Gwen McCaffrey, PhD,
  2. Thomas P. Davis, PhD
  1. From the Department of Medical Pharmacology, University of Arizona College of Medicine, Tucson, AZ.
  1. Received May 17, 2012.
  2. Accepted for publication September 12, 2012.
  3. Reprints: Gwen McCaffrey, PhD, Department of Medical Pharmacology College of Medicine, University of Arizona, 1501 N Campbell Ave, Tucson, AZ 85745. E-mail: gwenm{at}email.arizona.edu.
  4. This work was supported by National Institutes of Health grants R01-NS 39592, R01-NS42652, and R01-DA12684 to T.P.D. and CA 09820-0251 to G.M. The symposium was supported in part by a grant from the National Center for Research Resources (R13 RR023236).
  5. The authors declare that they do not have a financial interest conflict related to this work.

P-Glycoprotein and Occludin Trafficking as Therapeutic Targets to Optimize Central Nervous System Drug Delivery

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.

Key Words
  • blood-brain barrier
  • CNS drug delivery
  • protein trafficking
  • protein-protein interaction
  • oxidative stress
  • peripheral inflammatory pain
  • P-glycoprotein
  • occludin

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