“You Shall Not Pass”—tight junctions of the blood brain barrier

The blood-brain barrier (BBB) restricts diffusion between the central nervous system and systemic circulation, which is important in both health and disease. Excessive leakage across the BBB can harm nervous tissue, while a fully functional BBB can prevent therapeutic agents from reaching the brain. The BBB relies on tight junctions (TJs) between cells, which control paracellular diffusion. Understanding how these TJs form and function is crucial for developing strategies to deliver drugs to the CNS in a controlled manner. This review discusses the establishment of the BBB during embryonic development, detailing the ultrastructure, biogenesis, and molecular composition of epithelial and endothelial TJs.

• 1
  BBB formation is a complex process involving various cell types, including endothelial cells, astrocytes, neurons, glial cells, and pericytes, requiring their concerted action and interaction.
• 2
  Tight junctions, particularly those sealing the microvascular endothelium, are central to the BBB's function, maintaining a size and charge-selective paracellular barrier.
• 3
  TJ-associated MARVEL proteins are able to partially exert redundant functions, but also show tissue-specific expression and are involved in distinct aspects of tight junction assembly, maintenance, and regulation.