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

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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 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.

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Abbreviations

AGEs:

Advanced glycation end products

APP:

Amyloid precursor protein

CAT:

Catalase

GR:

Glutathione reductase

GSH-Px:

Glutathione peroxidase

IL-1β:

Interleukin-1beta

MDA:

Malondialdehyde

RAGE:

AGEs receptor

ROSs:

Reactive oxygen species

SOD:

Superoxide dismutase

TNF-α:

Necrosis factor-α

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Acknowledgments

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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    Authors and Affiliations

    1. Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China

      Yan Hong, Chao Shen, Qingqing Yin, Menghan Sun, Yingjuan Ma & Xueping Liu

    2. Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, People’s Republic of China

      Xueping Liu

    3. Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, People’s Republic of China

      Xueping Liu

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    1. Yan Hong
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    Correspondence to Xueping Liu.

    Additional information

    Yan Hong and Chao Shen have contributed equally to this study.

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    Hong, Y., Shen, C., Yin, Q. et al. Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus. Neurochem Res 41, 1192–1199 (2016). https://doi.org/10.1007/s11064-015-1814-8

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    • DOI: https://doi.org/10.1007/s11064-015-1814-8

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