GIST Scholar
College of Life Sciences and Medical Engineering
Department of Life Sciences
1. Journal Articles
RAGE mediated intracellular A beta uptake contributes to the breakdown of tight junction in retinal pigment epithelium
- Type
- Article
- Citation
- Oncotarget, v.6, no.34, pp.35263 - 35273
- Issued Date
- 2015-11
- Abstract
- Intracellular amyloid beta (A beta) has been implicated in neuronal cell death in Alzheimer's disease (AD). Intracellular A beta also contributes to tight junction breakdown of retinal pigment epithelium (RPE) in age-related macular degeneration (AMD). Although A beta is predominantly secreted from neuronal cells, the mechanism of A beta transport into RPE remains to be fully elucidated. In this study, we demonstrated that intracellular A beta was found concomitantly with the breakdown of tight junction in RPE after subretinal injection of A beta into the mouse eye. We also presented evidence that receptor for advanced glycation end products (RAGE) contributed to endocytosis of A beta in RPE. siRNA-mediated knockdown of RAGE prevented intracellular A beta accumulation as well as subsequent tight junction breakdown in RPE. In addition, we found that RAGE-mediated p38 MAPK signaling contributed to endocytosis of A beta. Blockade of RAGE/p38 MAPK signaling inhibited A beta endocytosis, thereby preventing tight junction breakdown in RPE. These results implicate that intracellular A beta contributes to the breakdown of tight junction in RPE via the RAGE/p38 MAPK-mediated endocytosis. Thus, we suggest that RAGE could be a potential therapeutic target for intracellular A beta induced outer BRB breakdown in AMD.
- Publisher
- Impact Journals
- ISSN
- 1949-2553
- Appears in Collections:
- Department of Life Sciences > 1. Journal Articles
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