2. Academic Validation
  3. RP1, a RAGE antagonist peptide, can improve memory impairment and reduce Aβ plaque load in the APP/PS1 mouse model of Alzheimer's disease

RP1, a RAGE antagonist peptide, can improve memory impairment and reduce Aβ plaque load in the APP/PS1 mouse model of Alzheimer's disease

  • Neuropharmacology. 2020 Dec 1;180:108304. doi: 10.1016/j.neuropharm.2020.108304.
Yi-Yun Huang 1,  Nian Fang 2,  Hui-Ru Luo 3,  Feng Gao 4,  Yao Zou 5,  Li-Li Zhou 6,  Qing-Ping Zeng 7,  Shi-Song Fang 8,  Fei Xiao 9,  Qing Zheng 10
Affiliations

Affiliations

  • 1 Department of Microbial and Biochemical Pharmacy, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 2 Department of Microbial and Biochemical Pharmacy, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 3 Department of Microbial and Biochemical Pharmacy, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 4 Department of Microbial and Biochemical Pharmacy, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 5 Department of Microbial and Biochemical Pharmacy, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 6 Department of Microbial and Biochemical Pharmacy, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 7 Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: [email protected].
  • 8 Major Infectious Disease Control Key Laboratory, Key Reference Laboratory of Pathogen and Biosafety, Shenzhen Center for Disease Control and Prevention, Shenzhen, China. Electronic address: [email protected].
  • 9 Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 10 Department of Microbial and Biochemical Pharmacy, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: [email protected].
PMID: 32931813 DOI: 10.1016/j.neuropharm.2020.108304
Abstract

Amyloid-β (Aβ) accumulation is a pathological hallmark of Alzheimer's disease (AD). The receptor for advanced glycation end products (RAGE) is involved in the production and accumulation of Aβ. RP1, a peptide antagonist of RAGE, was screened by phage display technology in our previous studies, and its neuroprotective effects on an AD cell model have been confirmed. However, its efficacy in vivo remains unclear. Here, the intranasal delivery of RP1 to APPSwe/PS1dE9 (APP/PS1) mice significantly improved memory impairment and relieved the Aβ burden by decreasing the expression of amyloid precursor protein and β-secretase. RNA-sequencing (RNA-seq) was utilized to identify differentially expressed genes (DEGs) in APP/PS1 mice after RP1 administration. Several DEGs in RAGE downstream signalling pathways were downregulated. Some transcription factors (such as Fos) and the pathways enriched in the remarkable modules may also be related to the efficacy of RP1. In conclusion, RP1 significantly improves the AD symptoms of APP/PS1 mice, and the RNA-seq results provide new ideas for elucidating the possible mechanisms of RP1 treatment.

Keywords

Alzheimer's disease; Amyloid-β; Nasal administration; RNA-sequencing; Receptor for advanced glycation end products (RAGE).

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