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Updated: May 17, 2025

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Interaction Between Glucagon-like Peptide 1 and Its Analogs with Amyloid-β Peptide Affects Its Fibrillation and

Ekaterina A Litus1, Marina P Shevelyova1, Alisa A Vologzhannikova1

  • 1Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia.

International Journal of Molecular Sciences
|May 14, 2025
PubMed

Insights

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) directly interact with amyloid-beta (Aβ) peptides, modulating Aβ

Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Antidiabetic drugs, specifically GLP-1RAs, show therapeutic potential in Alzheimer's disease (AD) by influencing amyloid-beta (Aβ) metabolism.
  • Direct interactions between GLP-1RAs and Aβ, and their functional outcomes, are not well understood.

Purpose of the Study:

  • To investigate the direct binding interactions between GLP-1(7-37) and its analogs (semaglutide, liraglutide, exenatide) and monomeric Aβ40/Aβ42.
  • To explore the functional consequences of these interactions on Aβ fibrillation and cytotoxicity.

Main Methods:

  • Biolayer interferometry and surface plasmon resonance spectroscopy were used to study molecular interactions.
  • Dynamic light scattering assessed the quaternary structure of GLP-1RAs.
  • Thioflavin T assay, electron microscopy, and MTT assay evaluated Aβ fibrillation and cytotoxicity.

Main Results:

  • Direct binding was observed between GLP-1(7-37), semaglutide, liraglutide, and exenatide with monomeric Aβ40 and Aβ42, with liraglutide showing the highest affinity.
  • GLP-1RAs exhibited oligomerization tendencies.
  • GLP-1(7-37) and exenatide inhibited Aβ40 fibrillation; semaglutide promoted it.
  • GLP-1 analogs reduced Aβ cytotoxicity, but GLP-1(7-37) increased Aβ40 cytotoxicity.

Conclusions:

  • GLP-1RAs directly bind to Aβ peptides.
  • These interactions differentially affect Aβ fibrillation and cytotoxicity, indicating complex modulatory roles.
  • Further in vivo studies are warranted to explore these observed effects in the context of Alzheimer's disease.
Keywords:
Alzheimer’s diseaseAβ cytotoxicityAβ fibrillationamyloid-β peptide (Aβ)diabetes mellitusexenatideglucagon-like peptide-1liraglutideprotein–protein interactionsemaglutide

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