1. Academic Validation
  2. A glycine-serine-alanine-rich peptide ameliorates Alzheimer-type neurodegeneration

A glycine-serine-alanine-rich peptide ameliorates Alzheimer-type neurodegeneration

  • Br J Pharmacol. 2023 Feb 2. doi: 10.1111/bph.16048.
Si-Yuan Yao 1 Jia-Fan Wang 1 Zheng Xu 1 Yue Meng 1 Yue Xue 1 Fan Yang 1 Wen-Bing Yao 1 Xiang-Dong Gao 1 Song Chen 1
Affiliations

Affiliation

  • 1 Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China.
Abstract

Background and purpose: Repeated amino acid sequences are widely existing, and the glycine-serine-alanine repeat is an element with the similar general propensity of key pathological factors across neurodegenerative diseases to form β-sheet aggregation. The property of this repeat may shed LIGHT on exploration of disease-modifying therapies for neurodegenerative disease, however, its specific role and underlying mechanism remain largely unknown.

Experimental approach: Using transgenic mice and C. elegans, and rat and cell models of Alzheimer's disease (AD), we evaluated the actions of specific glycine-serine-alanine repeat peptide SNP especially SNP-9 on AD-like abnormalities. Entrance of SNP into brain, and SNP activity characteristic in neuronal cell and peptide entrance into cells were analyzed in the in vivo system and in vitro system respectively. The cell-free system and yeast two hybrid system were used to explore the potential target of SNP-9, and the cell-based system was used to confirm the interaction of the intracellular target with SNP-9.

Key results: Here, we first identify specific glycine-serine-alanine repeat peptide as neuroprotective peptide SNP, and propose SNP especially SNP-9 as potential therapeutic agent for the treatment of AD. SNP-9 can decrease oligomeric Aβ via co-assembling with the toxic Aβ oligomer to form heterooligomers. Furthermore, we identify calcyclin-binding protein as SNP-9 binding protein by screening of a human brain cDNA library, and confirm the vital role of calcyclin-binding protein in regulation of abnormal hyperphosphorylation of tau by SNP-9.

Conclusion: Our study provides foundations for development of glycine-serine-alanine repeat Peptides especially SNP-9 as potential therapeutic interventions for AD.

Keywords

Alzheimer's disease; Amyloid β; Calcyclin-binding protein; Glycine-serine-alanine repeat; Peptide; Tau.

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