Blood–brain barrier endothelial tight junction (BBB TJ) (BBB TJ)

The blood–brain barrier (BBB) endothelial tight junction is a specialized multicomponent protein complex that seals the space between endothelial cells in the brain's capillaries (Abbott et al., 2010). It is primarily composed of transmembrane proteins such as claudins (especially claudin-5), occludin, and junctional adhesion molecules (JAMs), which are anchored to the actin cytoskeleton by scaffold proteins like zonula occludens-1 (ZO-1) (Nitta et al., 2003; Stamatovic et al., 2016). These junctions are critical for maintaining the highly regulated microenvironment of the central nervous system by restricting the paracellular diffusion of ions, pathogens, and large molecules (Zlokovic, 2008). In many neurological disorders, including stroke, multiple sclerosis, and Alzheimer's disease, the degradation or reorganization of these junctions leads to barrier leakage, edema, and neuroinflammation (Daneman and Prat, 2015). Therapeutic strategies often target these junctions to either restore barrier integrity in disease or temporarily increase permeability for drug delivery, using agents like osmotic mannitol or claudin-5 modulators (Greene et al., 2020). However, pharmacological opening of these junctions presents safety challenges, including the risk of neurotoxicity from systemic substances and increased intracranial pressure (Huber et al., 2001).

Other names

Zonula occludensEndothelial tight junctionCerebrovascular tight junction

Osmotic disruption of junctional complexes and modulation of transmembrane protein interactions to increase paracellular permeability.