{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:54:31Z","timestamp":1784919271575,"version":"3.55.0"},"reference-count":73,"publisher":"SAGE Publications","issue":"s1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,4,22]]},"abstract":"<jats:p>Background: Familial Alzheimer\u2019s disease (FAD) is caused by mutations in one or more of 3 genes known as A\u03b2PP, PSEN1, and PSEN2. There are currently no effective therapies for FAD. Hence, novel therapeutics are needed. Objective: To analyze the effect of treatment with a combination of epigallocatechin-3-gallate (EGCG) and Melatonin (N-acetyl-5-methoxytryptamine, aMT) in a cerebral spheroid (CS) 3D in vitro model of PSEN 1 E280A FAD. Methods: We developed a CS in vitro model based on menstrual stromal cells derived from wild-type (WT) and mutant PSEN1 E280A menstrual blood cultured in Fast-N-Spheres V2 medium. Results: Beta-tubulin III, choline acetyltransferase, and GFAP in both WT and mutant CSs spontaneously expressed neuronal and astroglia markers when grown in Fast-N-Spheres V2 medium for 4 or 11 days. Mutant PSEN1 CSs had significantly increased levels of intracellular A\u03b2PP fragment peptides and concomitant appearance of oxidized DJ-1 as early as 4 days, and phosphorylated tau, decreased \u0394\u03a8m, and increased caspase-3 activity were observed on Day 11. Moreover, mutant CSs were unresponsive to acetylcholine. Treatment with a combination of EGCG and aMT decreased the levels of all typical pathological markers of FAD more efficiently than did EGCG or aMT alone, but aMT failed to restore Ca2+ influx in mutant CSs and decreased the beneficial effect of EGCG on Ca2+ influx in mutant CSs. Conclusion: Treatment with a combination of EGCG and aMT can be of high therapeutic value due to the high antioxidant capacity and anti-amyloidogenic effect of both compounds.<\/jats:p>","DOI":"10.3233\/jad-220903","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T11:22:10Z","timestamp":1677237730000},"page":"S51-S66","source":"Crossref","is-referenced-by-count":12,"title":["Neuroprotective Effect of Combined Treatment with Epigallocatechin 3-Gallate and Melatonin on Familial Alzheimer\u2019s Disease PSEN1 E280A Cerebral Spheroids Derived from Menstrual Mesenchymal Stromal Cells"],"prefix":"10.1177","volume":"99","author":[{"given":"Viviana","family":"Soto-Mercado","sequence":"first","affiliation":[{"name":"Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, University of Antioquia, SIU Medellin, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Mendivil-Perez","sequence":"additional","affiliation":[{"name":"Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, University of Antioquia, SIU Medellin, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0557-0411","authenticated-orcid":false,"given":"Carlos","family":"Velez-Pardo","sequence":"additional","affiliation":[{"name":"Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, University of Antioquia, SIU Medellin, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-2386","authenticated-orcid":false,"given":"Marlene","family":"Jimenez-Del-Rio","sequence":"additional","affiliation":[{"name":"Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, University of Antioquia, SIU Medellin, 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