{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:15:20Z","timestamp":1790252120387,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019379","name":"Chulabhorn Graduate Institute","doi-asserted-by":"crossref","award":["651-AB01"],"award-info":[{"award-number":["651-AB01"]}],"id":[{"id":"10.13039\/100019379","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Stroke and Alzheimer\u2019s disease (AD) are prevalent age-related diseases; however, the relationship between these two diseases remains unclear. In this study, we aimed to investigate the ability of melatonin, a hormone produced by the pineal gland, to alleviate the effects of ischemic stroke leading to AD by observing the pathogenesis of AD hallmarks. We utilized SH-SY5Y cells under the conditions of oxygen\u2013glucose deprivation (OGD) and oxygen-glucose deprivation and reoxygenation (OGD\/R) to establish ischemic stroke conditions. We detected that hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), an indicator of ischemic stroke, was highly upregulated at both the protein and mRNA levels under OGD conditions. Melatonin significantly downregulated both HIF-1\u03b1 mRNA and protein expression under OGD\/R conditions. We detected the upregulation of \u03b2-site APP-cleaving enzyme 1 (BACE1) mRNA and protein expression under both OGD and OGD\/R conditions, while 10 \u00b5M of melatonin attenuated these effects and inhibited beta amyloid (A\u03b2) production. Furthermore, we demonstrated that OGD\/R conditions were able to activate the BACE1 promoter, while melatonin inhibited this effect. The present results indicate that melatonin has a significant impact on preventing the aberrant development of ischemic stroke, which can lead to the development of AD, providing new insight into the prevention of AD and potential stroke treatments.<\/jats:p>","DOI":"10.3390\/ijms25105225","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:03:08Z","timestamp":1715673788000},"page":"5225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Melatonin Inhibits Hypoxia-Induced Alzheimer\u2019s Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-5189","authenticated-orcid":false,"given":"Nongnuch","family":"Singrang","sequence":"first","affiliation":[{"name":"Chulabhorn Graduate Institute, Bangkok 10210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chutikorn","family":"Nopparat","sequence":"additional","affiliation":[{"name":"Innovative Learning Center, Srinakharinwirot University, Bangkok 10110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1541-7995","authenticated-orcid":false,"given":"Jiraporn","family":"Panmanee","sequence":"additional","affiliation":[{"name":"Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyarat","family":"Govitrapong","sequence":"additional","affiliation":[{"name":"Chulabhorn Graduate Institute, Bangkok 10210, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hathidara, M.Y., Saini, V., and Malik, A.M. 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