{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:27:32Z","timestamp":1778837252608,"version":"3.51.4"},"reference-count":87,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-74-10072"],"award-info":[{"award-number":["20-74-10072"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s disease (AD) by modulating amyloid-\u03b2 peptide (A\u03b2) metabolism. Meanwhile, the direct interactions between GLP-1RAs and A\u03b2 and their functional consequences remain unexplored. In this study, the interactions between monomeric A\u03b240\/A\u03b242 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 A\u03b2 fibrillation were assessed using the thioflavin T assay and electron microscopy. The impact of GLP-1RAs on A\u03b2 cytotoxicity was evaluated via the MTT assay. Monomeric A\u03b240 and A\u03b242 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\u201360 nM). GLP-1RAs are prone to oligomerization, which may affect their binding to A\u03b2. GLP-1(7-37) and Exen inhibit A\u03b240 fibrillation, whereas Sema promotes it. GLP-1 analogs decrease A\u03b2 cytotoxicity toward SH-SY5Y cells, while GLP-1(7-37) enhances A\u03b240 cytotoxicity without affecting the cytotoxic effect of A\u03b242. Overall, GLP-1RAs interact with A\u03b2 and differentially modulate its fibrillation and cytotoxicity, suggesting the need for further studies of our observed effects in vivo.<\/jats:p>","DOI":"10.3390\/ijms26094095","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:42:09Z","timestamp":1745577729000},"page":"4095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Interaction Between Glucagon-like Peptide 1 and Its Analogs with Amyloid-\u03b2 Peptide Affects Its Fibrillation and Cytotoxicity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7459-6295","authenticated-orcid":false,"given":"Ekaterina A.","family":"Litus","sequence":"first","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7638-5143","authenticated-orcid":false,"given":"Marina P.","family":"Shevelyova","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5550-2129","authenticated-orcid":false,"given":"Alisa A.","family":"Vologzhannikova","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgenia I.","family":"Deryusheva","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina V.","family":"Chaplygina","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8801-3786","authenticated-orcid":false,"given":"Victoria A.","family":"Rastrygina","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4859-7219","authenticated-orcid":false,"given":"Andrey V.","family":"Machulin","sequence":"additional","affiliation":[{"name":"Skryabin Institute of Biochemistry and Physiology of Microorganisms, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria D.","family":"Alikova","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliya A.","family":"Nazipova","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E.","family":"Permyakova","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7163-0497","authenticated-orcid":false,"given":"Victor V.","family":"Dotsenko","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technologies, Kuban State University, 149 Stavropolskaya St., 350040 Krasnodar, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4086-3137","authenticated-orcid":false,"given":"Sergei E.","family":"Permyakov","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, 142290 Pushchino, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina L.","family":"Nemashkalova","sequence":"additional","affiliation":[{"name":"Institute for Biological Instrumentation, Pushchino 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