[EZ-Western serise] Intracellular amyloid-β disrupts tight junctions of the retinal pigment epithelium via NF-κB activation
- - 짧은주소 : http://www.dogenbio.com/bbs/?t=aK
- - 년도 : 2020
- - 제품명 : EZ-Western Lumi Pico
- - 학술지명 : Neurobiology of Aging
- - 주소링크 : https://www.sciencedirect.com/science/article/abs/pii/S019745802030229…
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-β is one of the important components of drusen, which leads to local inflammation. Furthermore, intracellular amyloid-β disrupts tight junctions of the RPE. However, the intracellular mechanisms linking intracellular amyloid-β and tight-junction disruption are not clear. In this study, intracellular amyloid-β oligomers activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, leading to the disorganization of tight junctions of the RPE in mice after subretinal injection of amyloid-β. Amyloid-β also triggered NF-κB activation in the RPE cells in confluent culture, which was inhibited by the suppression of the advanced glycosylation end product–specific receptor. NF-κB inhibition by an IκB 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-κB inhibition, although there were intracellular amyloid-β oligomers. These data suggested that NF-κB inhibition might be a therapeutic approach to prevent amyloid-β–mediated tight-junction disruption.