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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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

Author(s): Masaki Ueno

Volume 14 , Issue 11 , 2007

Page: [1199 - 1206] Pages: 8

DOI: 10.2174/092986707780597943

Price: $65

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, caveolae, circumventricular organ, clathrin, glycocalyx, P-glycoprotein, tight junction, vesicular transport


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