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It has been widely studied for its therapeutic effects on Alzheimer\u2019s disease (AD), particularly through the amyloidosis, oxidative stress, and neuroinflammation pathways. Nevertheless, the mechanisms through which it exerts its neuroprotective effects in AD are still largely unknown. Data mining was used to identify potential gene targets that link melatonin\u2019s effects to AD pathways, yielding a comprehensive view of the underlying molecular mechanisms. We identified 3397 genes related to AD from DisGeNet and 329 melatonin gene targets from ChEMBL, which revealed 223 overlapping genes and the potential shared pathways. These genes were used to construct a protein\u2013protein interaction (PPI) network comprising 143 nodes and 823 edges, which demonstrated significant PPI enrichment. A cluster analysis highlighted two key clusters centered on MMP2 and NR3C1, with both genes playing crucial roles in steroid hormone signaling, apoptosis, and monoamine neurotransmission. Gene Ontology (GO) enrichment and KEGG pathway analyses further elucidated their involvement in critical pathways, for instance, steroid hormone signaling and apoptosis regulation, significantly influencing AD pathology through mechanisms such as extracellular matrix remodeling, epigenetic modifications, and neuroinflammation. Our findings emphasize MMP2 and NR3C1 as important gene targets for future research on melatonin treatment in AD, paving the way for further investigations into their roles in AD pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms26010338","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T07:44:53Z","timestamp":1735803893000},"page":"338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Data Mining Approach to Melatonin Treatment in Alzheimer\u2019s Disease: New Gene Targets MMP2 and NR3C1"],"prefix":"10.3390","volume":"26","author":[{"given":"Jingyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1366-1284","authenticated-orcid":false,"given":"Ka Chun","family":"Tsui","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoi Ying","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-1536","authenticated-orcid":false,"given":"Luca","family":"Aquili","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"College of Science, Health, Engineering and Education, Discipline of Psychology, Murdoch University, Perth 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-4498","authenticated-orcid":false,"given":"Kah Hui","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersoy","family":"Kocabicak","sequence":"additional","affiliation":[{"name":"Atlas University, 34406 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Temel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Maastricht University, 6202 Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3442-1415","authenticated-orcid":false,"given":"Zhiliang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"Suzhou Municipal Key Laboratory of Cancer Biology and Chronic Diseases, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Lung","family":"Fung","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Kalueff","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6692-6285","authenticated-orcid":false,"given":"Lee Wei","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioinformatics, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"},{"name":"Atlas University, 34406 Istanbul, Turkey"},{"name":"Department of Neurosurgery, Maastricht University, 6202 Maastricht, The Netherlands"},{"name":"Suzhou Municipal Key Laboratory of Cancer Biology and Chronic Diseases, School of Science, Xi\u2019an Jiaotong-Liverpool University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2021). 2021 Alzheimer\u2019s disease facts and figures. 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