Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-beta Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus
作者
Hong, Y;Shen, C;Yin, QQ;Sun, MH;Ma, YJ;Liu, XP
作者单位
[Hong, Yan; Shen, Chao; Yin, Qingqing; Sun, Menghan; Ma, Yingjuan; Liu, Xueping] Shandong Univ, Prov Hosp, Dept Senile Neurol, 324 Jing Wu Rd, Jinan 250021, Peoples R China.;-;[Liu, Xueping] Shandong Univ, Prov Hosp, Dept Antiaging, 324 Jing Wu Rd, Jinan 250021, Peoples R China.;-;[Liu, Xueping] Shandong Univ, Prov Hosp, Antiaging Monitoring Lab, 324 Jing Wu Rd, Jinan 250021, Peoples R China.
摘要
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-beta 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.
关键词
GLYCATION END-PRODUCTS; ALZHEIMERS-DISEASE; MOUSE MODEL; KAPPA-B; RECEPTOR; ACTIVATION; INVOLVEMENT; EXPRESSION; NEURONS; NEUROINFLAMMATION
基本信息
