title: Tight junction modulation of the blood brain barrier: CNS delivery of small molecules.
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.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin ; Dublin 2, Ireland.
authors.forename: Chris
authors.initials: C
authors.lastname: Greene
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin ; Dublin 2, Ireland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Campbell
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002199:Capillary Permeability; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D062725:Tight Junction Proteins