TABLE 1.

Contribution of tight junction components to disease pathology.

Tight junction component	Disease pathology
Claudin-5	• EAE/MS: claudin-5 loss and remodeling during leukocyte transmigration • RPE atrophy observed in response to claudin-5 downregulation (animal model of dry AMD) • Decreased claudin-5 levels detected in post-mortem brains of individuals diagnosed with Schizophrenia • Decreased claudin-5 levels found in Epilepsy • Stroke • Cold-induced model of traumatic brain injury (TBI) found decreased claudin-5 levels reduced edema and accelerated recovery • Repetitive mild TBI found decreased claudin-5 levels in association with deposition of hyperphosphorylated tau leading to BBB dysfunction • Alzheimer’s disease found increased amyloid-β clearance into blood when claudin-5 and occluding down-regulated. • Claudin-5 knockdown exacerbates social defeat model of depression • Claudin-5 mislocalization and increased expression in oxygen induced retinopathy (OIR) model
Claudin-1	• Increased expression in stroke • Decreased expression in Glioblastoma Multiforme • Expression of claudin-1 reduces vascular leakage in model of EAE
Claudin-3	• Decreased expression observed in EAE and Glioblastoma Multiforme
Occludin	• Lower occludin levels observed in Multiple Sclerosis • VEGF mediated phosphorylation of occludin in Diabetic Retinopathy leads to dysfunctional iBRB • Alzheimer’s disease found increased amyloid-β clearance into blood when claudin-5 and occludin down-regulated
Zonula Occludens (ZO-1)	• In Multiple Sclerosis lesions ZO-1 expression reduced leading to junctional instability
LSR	• Downregulated in EAE/middle cerebral artery occlusion leading to junctional instability
JAM-A	• Loss of JAM-A leads to increased neutrophil transmigration • Increased JAM-A expression correlates with increased monocyte migration in HIV-infected individuals
JAM-C	• Down-regulation of JAM-C inhibits wet AMD patient macrophage adhesion to endothelial cells