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Neurochem Res. 2016 May;41(5):1192-9. doi: 10.1007/s11064-015-1814-8. Epub 2016 Jan 6.

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

Hong Y1, Shen C1, Yin Q1, Sun M1, Ma Y1, Liu X2,3,4.

Author information

1
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
2
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China. yinyunqing11@126.com.
3
Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, People's Republic of China. yinyunqing11@126.com.
4
Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, People's Republic of China. yinyunqing11@126.com.

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.

KEYWORDS:

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

PMID:
26738988
DOI:
10.1007/s11064-015-1814-8
[Indexed for MEDLINE]

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