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Tight Junction Modulation of the Blood Brain Barrier: CNS Delivery of Small Molecules

Overview
Journal Tissue Barriers
Date 2016 May 4
PMID 27141420
Citations 107
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Abstract

The blood brain barrier (BBB) represents a major obstacle for targeted drug delivery to the brain for the treatment of central nervous system (CNS) disorders. Significant advances in barrier research over the past decade has led to the discovery of an increasing number of structural and regulatory proteins in tight junctions (TJ) and adherens junctions (AJ). These discoveries are providing the framework for the development of novel TJ modulators which can act specifically and temporarily to alter BBB function and regulate paracellular uptake of molecules. TJ modulators that have shown therapeutic potential in preclinical models include claudin-5 and occludin siRNAs, peptides derived from zonula occludens toxin as well as synthetic peptides targeting the extracellular loops of TJs. Adding to the array of modulating agents are novel mechanisms of BBB regulation such as focused ultrasound (FUS). This review will give a succinct overview of BBB biology and TJ modulation in general. Novel insights into BBB regulation in health and disease will also be summarized.

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References
1.
Butt A, JONES H, Abbott N . Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study. J Physiol. 1990; 429:47-62. PMC: 1181686. DOI: 10.1113/jphysiol.1990.sp018243. View

2.
Nguyen L, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X . Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature. 2014; 509(7501):503-6. DOI: 10.1038/nature13241. View

3.
Campbell M, Nguyen A, Kiang A, Tam L, Gobbo O, Kerskens C . An experimental platform for systemic drug delivery to the retina. Proc Natl Acad Sci U S A. 2009; 106(42):17817-22. PMC: 2760489. DOI: 10.1073/pnas.0908561106. View

4.
Saunders N, Liddelow S, Dziegielewska K . Barrier mechanisms in the developing brain. Front Pharmacol. 2012; 3:46. PMC: 3314990. DOI: 10.3389/fphar.2012.00046. View

5.
Itoh M, Sasaki H, Furuse M, Ozaki H, Kita T, Tsukita S . Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions. J Cell Biol. 2001; 154(3):491-7. PMC: 2196413. DOI: 10.1083/jcb.200103047. View