{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:07:21Z","timestamp":1753877241762,"version":"3.41.2"},"reference-count":55,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2024QH384"],"award-info":[{"award-number":["ZR2024QH384"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shandong Provincial Hospital Research Incubation Fund","award":["2023FY061"],"award-info":[{"award-number":["2023FY061"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["823B2026"],"award-info":[{"award-number":["823B2026"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Presenilin 1 (PSEN1) mutations are the leading cause of early-onset Alzheimer disease (EOAD). A recent study found that the PSEN1 M139I mutation is associated with EOAD. In this study, we examined the impact of the PSEN1 M139I mutation in an EOAD in vitro model. Our findings reveal that the PSEN1 M139I mutation leads to increased levels of A\u03b242\/40, Hairy and Enhancer of Split-1 (Hes1), neurogenic locus notch homolog intracellular domain, and microRNA-34a, accompanied by a decrease in the level of neurogenic locus notch homolog protein 1 (NOTCH-1). Computational predictions indicate that NOTCH-1 is a direct target of microRNA-34a. Transfection of microRNA-34a mimics into PSEN1 M139I mutant SH-SY5Y cells increased the ratio of A\u03b242\/40 and induced Hes1, cysteine-aspartic acid protease 3 (Caspase-3), and apoptosis while reducing the NOTCH-1 expression and inhibiting cell proliferation. Conversely, downregulating microRNA-34a expression by transfecting microRNA-34a inhibitors mitigated these effects, thereby restoring NOTCH-1 production and cell proliferation and reversing the increases in A\u03b242\/40 ratio, Hes1, Caspase-3, and apoptosis induced by the PSEN1 M139I mutation. In summary, the PSEN1 M139I mutation identified in EOAD may influence amyloid-\u03b2 (A\u03b2) production and apoptosis by regulating the microRNA-34a-mediated NOTCH-1 signaling pathway.<\/jats:p>","DOI":"10.1093\/jnen\/nlaf044","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T21:06:59Z","timestamp":1745701619000},"source":"Crossref","is-referenced-by-count":0,"title":["Presenilin 1 M139I mutation regulates the microRNA-34a-mediated neurogenic locus notch homolog protein 1 signaling pathway in an early-onset Alzheimer disease cell model"],"prefix":"10.1093","author":[{"given":"Xuechun","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Neurology, Jinan Central Hospital Affiliated to Shandong First Medical University , Jinan,","place":["China"]},{"name":"Department of Neurology, Xuanwu Jinan Hospital , Jinan, Shandong,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijun","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University , Wuhan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lufeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Linyi People\u2019s Hospital , Linyi,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Record Information Section, Yantai Yuhuangding Hospital , 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