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Interaction Between Glucagon-like Peptide 1 and Its Analogs with Amyloid-β Peptide Affects Its Fibrillation and Cytotoxicity
Litus EA, Shevelyova MP, Vologzhannikova AA, Deryusheva EI, Chaplygina AV, Rastrygina VA, Machulin AV, Alikova VD et al.. International journal of molecular sciences, 2025-04-25
Topic: Brain proteins, microglia and lab models
Clinical data as well as animal and cell studies indicate that certain antidiabetic drugs, including glucagon-like peptide 1 receptor agonists (GLP-1RAs), exert therapeutic effects in Alzheimer's disease (AD) by modulating amyloid-β peptide (Aβ) metabolism. Meanwhile, the direct interactions between GLP-1RAs and Aβ and their functional consequences remain unexplored. In this study, the interactions between monomeric Aβ40/Aβ42 of GLP-1(7-37) and its several analogs (semaglutide (Sema), liraglutide (Lira), exenatide (Exen)) were studied using biolayer interferometry and surface plasmon resonance spectroscopy. The quaternary structure of GLP-1RAs was investigated using dynamic light scattering. The effects of GLP-1RAs on Aβ fibrillation were assessed using the thioflavin T assay and electron microscopy. The impact of GLP-1RAs on Aβ cytotoxicity was evaluated via the MTT assay. Monomeric Aβ40 and Aβ42 directly bind to GLP-1(7-37), Sema, Lira, and Exen, with the highest affinity for Lira (the lowest estimates of equilibrium dissociation constants were 42-60 nM). GLP-1RAs are prone to oligomerization, which may affect their binding to Aβ. GLP-1(7-37) and Exen inhibit Aβ40 fibrillation, whereas Sema promotes it. GLP-1 analogs decrease Aβ cytotoxicity toward SH-SY5Y cells, while GLP-1(7-37) enhances Aβ40 cytotoxicity without affecting the cytotoxic effect of Aβ42. Overall, GLP-1RAs interact with Aβ and differentially modulate its fibrillation and cytotoxicity, suggesting the need for further studies of our observed effects in vivo.
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APA 7th
Litus, E. A., Shevelyova, M. P., Vologzhannikova, A. A., Deryusheva, E. I., Chaplygina, A. V., Rastrygina, V. A., et al. (2025). Interaction Between Glucagon-like Peptide 1 and Its Analogs with Amyloid-β Peptide Affects Its Fibrillation and Cytotoxicity. International journal of molecular sciences. https://doi.org/10.3390/ijms26094095
Vancouver
Litus EA, Shevelyova MP, Vologzhannikova AA, Deryusheva EI, Chaplygina AV, Rastrygina VA, et al. Interaction Between Glucagon-like Peptide 1 and Its Analogs with Amyloid-β Peptide Affects Its Fibrillation and Cytotoxicity. International journal of molecular sciences. 2025. doi:10.3390/ijms26094095. PMID: 40362335.
BibTeX
@article{litus2025-40362335,
author = {Litus, E. A. and Shevelyova, M. P. and Vologzhannikova, A. A. and Deryusheva, E. I. and Chaplygina, A. V. and Rastrygina, V. A. and Machulin, A. V. and Alikova, V. D. and others},
title = {{Interaction Between Glucagon-like Peptide 1 and Its Analogs with Amyloid-β Peptide Affects Its Fibrillation and Cytotoxicity}},
journal = {International journal of molecular sciences},
year = {2025},
doi = {10.3390/ijms26094095},
pmid = {40362335},
url = {https://doi.org/10.3390/ijms26094095}
}
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Key findings
- Clinical data as well as animal and cell studies indicate that certain antidiabetic drugs, including glucagon-like peptide 1 receptor agonists (GLP-1RAs), exert therapeutic effects in Alzheimer's disease (AD) by modulating amyloid-β peptide (Aβ) metabolism.
- Overall, GLP-1RAs interact with Aβ and differentially modulate its fibrillation and cytotoxicity, suggesting the need for further studies of our observed effects in vivo.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International journal of molecular sciences) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40362335) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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