Holey barrier: claudins and the regulation of brain endothelial permeability.
Endothelial tight junctions (TJs)* are an important functional part of the blood-brain barrier (BBB). In this issue, Nitta et al. (2003) demonstrate that claudin-5, a transmembrane protein of TJs, is a critical determinant of BBB permeability in mice. Unexpectedly, knockout of claudin-5 did not result in a general breakdown of TJs but in a selective increase in paracellular permeability of small molecules. This suggests that the BBB can be manipulated to allow selective diffusion of small molecules and makes claudin-5 a possible target for the development of drugs for this purpose.
Division of Cell Biology, Institute of Ophthalmology, University College London, UK. k.matter@ucl.ac.uk
Karl
K
Matter
Maria S
MS
Balda
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000235:genetics*; D001921:Brain / Q000098:blood supply*; D002462:Cell Membrane / Q000378:metabolism; D062507:Claudin-5; D015195:Drug Design; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D015202:Protein Engineering; D019108:Tight Junctions / Q000378:metabolism*
C107466:CLDN5 protein, human; D062507:Claudin-5; C491511:Cldn5 protein, mouse; D008565:Membrane Proteins