The region‐selective regulation of endothelial claudin‐5 expression and signaling in brain health and disorders

Abstract The neurovascular unit (NVU) consists of neurons, glial cells, microvascular cells, and extracellular matrix, and is involved in a variety of physiological and pathological processes in the central nervous system (CNS). Within the NVU, the microvascular endothelial cells and pericytes principally contribute to maintaining the integrity of the blood–brain barrier (BBB). Various types of cells are connected to each other in the NVU by diverse cell adhesion molecules, of which claudin‐5 (CLDN5) is by far the most abundantly expressed tight‐junction protein in brain microvascular endothelial cells and absolutely required for the maintenance of the BBB. This review highlights recent progress in understanding the region‐specific regulation and dysregulation of CLDN5 expression in CNS health and disorders. We also discuss how CLDN5 expression is regionally disrupted within the NVU. In addition, we focus on the link between cell adhesion and transcription factor signalings and describe the possible involvement of CLDN5‐adhesion signaling in brain health and disorders.