{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:27:34Z","timestamp":1793284054405,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To analyze the expressional changes in the PI3K\/Akt\/GSK\u20103\u03b2 pathway and metalloprotease in the cellular Alzheimer's Disease (AD) model with the effect of antioxidant resveratrol. Neuron\u2010like cells were obtained by a two\u2010step method of neuronal differentiation by using a combination of retinoic acid (RA) and brain\u2010derived factor (BDNF) exposure. Then, the application of the amyloid beta peptide 25\u201335 (A\u03b225\u201035) to the cell culture mimicked the environmental toxicity observed in AD. Afterward, cell viability and apoptosis assays were performed to determine whether the resveratrol exerts a cytotoxic and apoptotic effect. Finally, the expressional changes in genes in the cellular AD model with the effect of resveratrol were analyzed by Real\u2010Time PCR. The analysis in silico was assessed using the STRING V12.0 database in each group. Apoptosis data findings were decreased by 1.5\u2010fold and 2.5\u2010fold respectively by Differentiated+Resveratrol (RES) and RES when compared to control but no significant difference was observed between RES and AD model groups. Real\u2010time PCR analysis results revealed PI3K (3.38\u2010fold), AKT (3.95\u2010fold), and RELN (1.99\u2010fold) expressions were significantly higher (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001), and also GSK\u20103\u03b2, TAU, ADAMTS\u20104, ADAMTS\u20105, and TIMP\u20103 gene expression levels were significantly downregulated (2.53\u2010, 1.79\u2010, 2.85\u2010, 4.09\u2010, and 6.62\u2010fold, respectively) in the Differentiated+A\u03b2\u2009+\u2009RES groups compared to the Differentiated+A\u03b2 group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.001). Network analysis shows the functional enrichment of 23 Alzheimer\u2010related GO terms in the Wnt signaling, proteolysis, and extracellular matrix organization pathways. Resveratrol has inhibited GSK\u20103\u03b2 by activating the PI3K\/Akt insulin pathway in a neurotoxic environment. In addition, TAU, RELN, metalloproteases, and their inhibitors associated with Alzheimer's pathology have been regulated supporting the neuroprotective effect of resveratrol.\n                  <\/jats:p>","DOI":"10.1002\/iub.2902","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T12:58:54Z","timestamp":1724072334000},"page":"1199-1208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neuroprotective effects of resveratrol through modulation of\n                    <scp>PI3K<\/scp>\n                    \/Akt\/\n                    <scp>GSK<\/scp>\n                    \u20103\u03b2 pathway and metalloproteases"],"prefix":"10.1002","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4939-9270","authenticated-orcid":false,"given":"L\u00fctfiye","family":"Ozpak","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Sut\u00e7u Imam University  Kahramanmara\u015f Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakiye G\u00f6ker","family":"Ba\u011fca","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Ayd\u0131n Adnan Menderes University  Ayd\u0131n Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13439"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.12.024"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052687"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02611-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v6.i12.1223"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9459-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2019.103401"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2012.1525"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.619024"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2008.11.001"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10050737"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11010126"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2020.1754211"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-016-1886-0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules190812242"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040721"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094628"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153664"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2018.06.001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23092328"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12192-021-01231-3"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-017-2421-7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-018-2683-8"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.13601"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0234632"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1556\/2060.2023.00170"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181883883"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20190126"}],"container-title":["IUBMB 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