title: The potential mechanisms of Aβ-receptor for advanced glycation end-products interaction disrupting tight junctions of the blood-brain barrier in Alzheimer's disease.
abstract: The receptor for advanced glycation end-products (RAGE) is a multiligand membrane receptor that has been implicated in the cytotoxicity effects of β-amyloid protein (Aβ) in AD. Positive feedback mechanism of RAGE within blood-brain barrier (BBB) and/or cells inside the brain is proposed, including interaction with Aβ 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 Aβ cytotoxicity. Attenuation of RAGE activity may inhibit Aβ 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 Aβ-RAGE interaction. Tight junctions (TJ) are identified as the basic structure of the BBB and RAGE-mediated Aβ cytotoxicity to the brain microvascular endothelial cells (BMEC), resulting in damaged BBB structural integrity. However, the potential mechanism is poorly studied.
authors.affiliation: Huadong Hospital, Fudan University , Shanghai , PR China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wan
authors.forename: Huixian
authors.initials: H
authors.lastname: Chen
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D058990:Molecular Targeted Therapy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic