A tight regulation of the neuroparenchymal microenvironment is imperative for proper neurological function. The flux of blood-borne ions and solutes is restricted by specialized tissue barriers and of the three main CNS barriers the brain endothelium constituting the blood-brain barrier represents the major interface between the blood and the brain. At the basis of the BBB are, next to an elaborate transporting machinery, tight junctions which create not only a paracellular diffusion constraint but also enable the vectorial transport across the endothelial monolayer. Generally, TJs not only represent a cell-cell adhesion structure, but integrate various signaling pathways via large multi-protein complexes, thereby impacting upon processes such as cell proliferation, cytoskeletal rearrangement, and transcriptional control. This review provides an overview of TJ morphology and discusses our current understanding of the molecular composition of endothelial TJs at the BBB.
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