title: Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus.
abstract: An increased level of advanced glycation end products (AGEs) is observed in brains of patients with Alzheimer's disease (AD). AGEs and receptor for AGEs (RAGE) play important roles in the pathogenesis of AD. FPS-ZM1 is a high-affinity RAGE-specific blocker that inhibits amyloid-β binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. In this study, an AGEs-RAGE-activated rat model were established by intrahippocampal injection of AGEs, then these rats were treated with intraperitoneal administration of FPS-ZM1 and the possible neuroprotective effects were investigated. We found that AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. Our results suggest that the AGEs-RAGE pathway is responsible for cognitive deficits, and therefore may be a potential treatment target. FPS-ZM1 might be a novel therapeutic agent to treat AD patients.
authors.affiliation: Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
authors.forename: Menghan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
authors.forename: Yingjuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China. yinyunqing11@126.com.|Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, People's Republic of China. yinyunqing11@126.com.|Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, People's Republic of China. yinyunqing11@126.com.
authors.forename: Xueping
authors.initials: X
authors.lastname: Liu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000523:psychology; D016207:Cytokines / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C000593874:Ager protein, rat; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001549:Benzamides; D016207:Cytokines; C572629:FPS-ZM1; D017127:Glycation End Products, Advanced; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; C075222:amyloid beta-protein (1-42); C000605560:amyloid beta-protein (11-40)
keywords: Advanced glycation end product; Alzheimer’s disease; Amyloid-β; FPS-ZM1; Inflammation; Oxidative stress; Receptor for advanced glycation end products