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Molecular Anatomy of the Brain Endothelial Barrier: An Overview of the Distributional Features

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Abstract:

The blood-brain barrier (BBB) impedes the influx of intravascular compounds from the blood to the brain. The elements composing the BBB are endothelial cells, pericytes and the end-feet of astrocytes. Among them, the endothelial cell barrier line is the most critical for preventing toxic substances from entering the brain. In this review, we focus on the ultrastructural distribution of important components in the intracellular junction and cytoplasm of brain endothelial cells. The ultrastructural distribution of tight junction-specific integral membrane proteins such as occludin, junctional adhesion molecules, claudin, peripheral zonula occludens protein-1 (ZO-1), adherens junction-specific transmembrane protein cadherin, and adherens junction-associated peripheral proteins α-catenin, β-catenin, and p120 catenin is reviewed. P-glycoprotein and some other transporters recently discovered in endothelial cells prevent several compounds from entering the brain parenchyma. It is likely that the transient inhibition of P-glycoprotein by antidepressants enables other medicines to enter the brain. Vesicular transport with clathrin-mediated or adsorptive endocytosis through endothelial cells is also critical for transportation of bloodborn substances from the bloodstream to the brain. How medicines pass the BBB to reach the brain parenchyma is discussed.

Keywords: Blood-brain barrier; P-glycoprotein; caveolae; circumventricular organ; clathrin; glycocalyx; tight junction; vesicular transport

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707780597943

Affiliations: Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho,Kita-gun, Kagawa 761-0793, Japan.

Publication date: May 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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