{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T08:29:23Z","timestamp":1786696163111,"version":"build-2736575974"},"reference-count":29,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and irreversible cognitive decline. Glycogen synthase kinase 3\u03b2 (GSK-3\u03b2) is significant in tau hyperphosphorylation and neurodegeneration. The cholinergic hypothesis of AD links cognitive impairment to reduced synaptic acetylcholine (ACh). Increased acetylcholinesterase (AChE) activity exacerbates this issue. To search for a potential dual GSK-3\u03b2\/AChE inhibitor, we focused on N-methylcytisine. This natural cytisine-derived alkaloid has not been studied for its various biological effects on the prevention of AD. The\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    results indicated that N-methylcytisine displayed promising activity against GSK-3\u03b2 and AChE with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 11 and 22.7\u202f\u00b5M, respectively. GSK-3\u03b2 kinetic study according to the varying substrate or ATP concentrations at different N-methylcytisine levels revealed mixed-type inhibition. The results of the integrated in\u00a0silico workflow indicate that N-methylcytisine exhibited favorable binding to AChE (docking score\u00a0\u22129.6\u202fkcal\/mol; MM-GBSA\u00a0\u221270.2\u202fkcal\/mol), comparable to the reference inhibitor galantamine (\u221210.8\u202fkcal\/mol;\u00a0\u221270.6\u202fkcal\/mol). In contrast, its interaction with GSK-3\u03b2 was more moderate (\u22125.3\u202fkcal\/mol;\u00a0\u221250.3\u202fkcal\/mol) relative to staurosporine (\u22128.5\u202fkcal\/mol;\u00a0\u221282.6\u202fkcal\/mol), consistent with its smaller scaffold. Overall, the results support a flexible, mixed-type interaction profile and highlight N-methylcytisine as a promising dual-acting candidate for Alzheimer\u2019s disease.\n                  <\/jats:p>","DOI":"10.1515\/biol-2025-1363","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:57:22Z","timestamp":1786694242000},"source":"Crossref","is-referenced-by-count":0,"title":["Dual inhibitory potential of N-methylcytisine against GSK-3\u03b2 and AChE: implications for Alzheimer\u2019s disease treatment"],"prefix":"10.1515","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7931-1546","authenticated-orcid":false,"given":"Shirin","family":"Tarbiat","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics , Uskudar University , 34662 Istanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-6668","authenticated-orcid":false,"given":"Nigar","family":"Kantarci-Carsibasi","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering , Uskudar University , 34662 Istanbul , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"2026081407571767780_j_biol-2025-1363_ref_001","doi-asserted-by":"crossref","unstructured":"Agarwal, U, Kapoor, G, Tonk, RK. 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