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

Gwen McCaffrey, Thomas P. Davis

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1131-1140
Number of pages10
JournalJournal of Investigative Medicine
Volume60
Issue number8
DOIs
Publication statusPublished - 2012

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Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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