Russian journal of bioorganic chemistry2022，Vol.48Issue(4) ：8.DOI:10.1134/S1068162022040197

Biologically Active Fragment of the Receptor for Advanced Glycation End Products (RAGE) Is Able to Inhibit Oligomerization of the Beta-Amyloid

Volkova, T. D. Avetisyan, A., V Koroev, D. O. Kamynina, A., V Balasanyants, S. M. Simonyan, R. A. Volpina, O. M.
Russian journal of bioorganic chemistry2022，Vol.48Issue(4) ：8.DOI:10.1134/S1068162022040197
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Biologically Active Fragment of the Receptor for Advanced Glycation End Products (RAGE) Is Able to Inhibit Oligomerization of the Beta-Amyloid

Volkova, T. D. 1Avetisyan, A., V 2Koroev, D. O. 1Kamynina, A., V 3Balasanyants, S. M. 4Simonyan, R. A. 2Volpina, O. M.1
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作者信息

  • 1. Russian Acad Sci
  • 2. Moscow MV Lomonosov State Univ
  • 3. Moscow Inst Phys & Technol Natl Res Univ
  • 4. Univ Illinois
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Abstract

It was found earlier that the synthetic fragment corresponding to the 60-76 sequence of the extracellular domain of the receptor for advanced glycation end products (RAGE) had a protective effect on animal and cellular models of Alzheimer's disease. It was proposed that this effect was mediated via the interaction of the peptide with beta-amyloid (A beta), which was one of the RAGE ligands, by inhibiting the formation of toxic A beta oligomers. The aim of this study was an application of physicochemical methods to an investigation of the ability of the 60-76 peptide to prevent the A beta 40 oligomerization in solution in comparison with the nonprotective 65-76 truncated peptide. The dynamics of the formation of the A beta 40 fibrils in the presence of the peptides was evaluated using thioflavin T. The relative sizes of oligomers were determined by dynamic light scattering. The peptide binding to A beta 40 was examined by fluorescence titration. We demonstrated by the two methods that the peptide corresponding to the 60-76 sequence of RAGE considerably inhibited (by more than 90%) the formation of oligomers and fibrils of A beta 40 distinct from the 65-76 peptide. In addition, we found that the protective effect of the peptides and their ability to inhibit the A beta 40 oligomerization did not correlate with their binding to the monomeric/tetrameric A beta 40. We confirmed in vitro the hypothesis that the protective activity of the synthetic 60-76 fragment of RAGE was associated with its ability to inhibit the A beta oligomerization.

Key words

receptor for the advanced glycation end products/synthetic peptides/Alzheimer's disease/beta-amyloid/oligomerization/dynamic light scattering/thioflavin T/PROTEIN A-BETA/ALZHEIMERS-DISEASE/SYNTHETIC FRAGMENT/MOUSE MODEL/BRAIN/A-BETA-40/MEMORY/FIBRILLOGENESIS/NEUROTOXICITY/A-BETA(1-42)

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出版年

2022
Russian journal of bioorganic chemistry

Russian journal of bioorganic chemistry

SCI
ISSN：1068-1620
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