| First Author | Jo DH | Year | 2020 |
| Journal | Neurobiol Aging | Volume | 95 |
| Pages | 115-122 | PubMed ID | 32795848 |
| Mgi Jnum | J:299583 | Mgi Id | MGI:6501321 |
| Doi | 10.1016/j.neurobiolaging.2020.07.013 | Citation | Jo DH, et al. (2020) Intracellular amyloid-beta disrupts tight junctions of the retinal pigment epithelium via NF-kappaB activation. Neurobiol Aging 95:115-122 |
| abstractText | Drusen are focal deposits between the retinal pigment epithelium (RPE) and Bruch's membrane in the retina of patients with age-related macular degeneration. Amyloid-beta is one of the important components of drusen, which leads to local inflammation. Furthermore, intracellular amyloid-beta disrupts tight junctions of the RPE. However, the intracellular mechanisms linking intracellular amyloid-beta and tight-junction disruption are not clear. In this study, intracellular amyloid-beta oligomers activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) p65, leading to the disorganization of tight junctions of the RPE in mice after subretinal injection of amyloid-beta. Amyloid-beta also triggered NF-kappaB activation in the RPE cells in confluent culture, which was inhibited by the suppression of the advanced glycosylation end product-specific receptor. NF-kappaB inhibition by an IkappaB kinase inhibitor prevented the suppression of expression of tight-junction proteins, zonula occuludens-1 and occludin in RPE cells. In addition, tight-junction complexes remained intact in the RPE of mice with NF-kappaB inhibition, although there were intracellular amyloid-beta oligomers. These data suggested that NF-kappaB inhibition might be a therapeutic approach to prevent amyloid-beta-mediated tight-junction disruption. |
