Tight junction modulation of the blood brain barrier: CNS delivery of small molecules

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 p...

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Bibliographic Details
Published inTissue barriers Vol. 4; no. 1; p. e1138017
Main Authors Greene, Chris, Campbell, Matthew
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 02.01.2016
Subjects
Animals
Blood-Brain Barrier - cytology
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
Capillary Permeability
Drug Carriers - administration & dosage
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Humans
Review
Tight Junction Proteins - metabolism
Tight Junctions - drug effects
Tight Junctions - metabolism
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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.
AbstractList 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.
Author Greene, Chris
Campbell, Matthew
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  surname: Campbell
  fullname: Campbell, Matthew
  email: Matthew.Campbell@tcd.ie
  organization: Smurfit Institute of Genetics, Trinity College Dublin
BackLink https://www.ncbi.nlm.nih.gov/pubmed/27141420$$D View this record in MEDLINE/PubMed
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Snippet 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....
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SubjectTerms Animals
Blood-Brain Barrier - cytology
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
Capillary Permeability
Drug Carriers - administration & dosage
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Humans
Review
Tight Junction Proteins - metabolism
Tight Junctions - drug effects
Tight Junctions - metabolism
Title Tight junction modulation of the blood brain barrier: CNS delivery of small molecules
URI https://www.tandfonline.com/doi/abs/10.1080/21688370.2015.1138017
https://www.ncbi.nlm.nih.gov/pubmed/27141420
https://pubmed.ncbi.nlm.nih.gov/PMC4836485
Volume 4
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