The potential mechanisms of Aβ-receptor for advanced glycation end-products interaction disrupting tight junctions of the blood-brain barrier in Alzheimer's disease

The receptor for advanced glycation end-products (RAGE) is a multiligand membrane receptor that has been implicated in the cytotoxicity effects of beta-amyloid protein (A beta) in AD. Positive feedback mechanism of RAGE within blood-brain barrier (BBB) and/or cells inside the brain is proposed, including interaction with A beta stimulating activation of proinflammatory cytokines, release of reactive oxygen species (ROS), which leads to neuron damage and BBB dysfunction. RAGE is the main factor mediating A beta cytotoxicity. Attenuation of RAGE activity may inhibit A beta from accumulation in the cerebral blood vessels and prevent neurotoxicity. Furthermore, RAGE may serve as a therapeutic target for Alzheimer's disease by inhibiting pathophysiological consequences of A beta-RAGE interaction. Tight junctions (TJ) are identified as the basic structure of the BBB and RAGE-mediated A beta cytotoxicity to the brain microvascular endothelial cells (BMEC), resulting in damaged BBB structural integrity. However, the potential mechanism is poorly studied.