Neurochemical Research

, Volume 41, Issue 5, pp 1192–1199 | Cite as

Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus

  • Yan Hong
  • Chao Shen
  • Qingqing Yin
  • Menghan Sun
  • Yingjuan Ma
  • Xueping LiuEmail author
Original Paper


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 APPsw/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.


Alzheimer’s disease Advanced glycation end product Receptor for advanced glycation end products FPS-ZM1 Amyloid-β Inflammation Oxidative stress 



Advanced glycation end products


Amyloid precursor protein




Glutathione reductase


Glutathione peroxidase






AGEs receptor


Reactive oxygen species


Superoxide dismutase


Necrosis factor-α



This study was supported by grants from the National Natural Science Foundation of China (No. 30971036) and Shandong Provincial Natural Science Foundation of China (No. Y2008C13).


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yan Hong
    • 1
  • Chao Shen
    • 1
  • Qingqing Yin
    • 1
  • Menghan Sun
    • 1
  • Yingjuan Ma
    • 1
  • Xueping Liu
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Senile NeurologyProvincial Hospital Affiliated to Shandong UniversityJinanChina
  2. 2.Department of Anti-AgingProvincial Hospital Affiliated to Shandong UniversityJinanPeople’s Republic of China
  3. 3.Anti-Aging Monitoring LaboratoryProvincial Hospital Affiliated to Shandong UniversityJinanPeople’s Republic of China

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