{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T16:50:18Z","timestamp":1793033418398,"version":"4.5.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005851","name":"shahid Beheshti university of medical sciences","doi-asserted-by":"publisher","award":["43007175-1"],"award-info":[{"award-number":["43007175-1"]}],"id":[{"id":"10.13039\/501100005851","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The association between Alzheimer\u2019s disease and metabolic disorders as significant risk factors is widely acknowledged. However, the intricate molecular mechanism intertwining these conditions remains elusive. To address this knowledge gap, we conducted a thorough investigation using a bioinformatics method to illuminate the molecular connections and pathways that provide novel perspectives on these disorders\u2019 pathological and clinical features. Microarray datasets (GSE5281, GSE122063) from the Gene Expression Omnibus (GEO) database facilitated the way to identify genes with differential expression in Alzheimer\u2019s disease (141 genes). Leveraging CoreMine, CTD, and Gene Card databases, we extracted genes associated with metabolic conditions, including hypertension, non-alcoholic fatty liver disease, and diabetes. Subsequent analysis uncovered overlapping genes implicated in metabolic conditions and Alzheimer\u2019s disease, revealing shared molecular links. We utilized String and HIPPIE databases to visualize these shared genes\u2019 protein-protein interactions (PPI) and constructed a PPI network using Cytoscape and MCODE plugin. SPP1, CD44, IGF1, and FLT1 were identified as crucial molecules in the main cluster of Alzheimer\u2019s disease and metabolic syndrome. Enrichment analysis by the DAVID dataset was employed and highlighted the SPP1 as a novel target, with its receptor CD44 playing a significant role in the inflammatory cascade and disruption of insulin signaling, contributing to the neurodegenerative aspects of Alzheimer\u2019s disease. ECM-receptor interactions, focal adhesion, and the PI3K\/Akt pathways may all mediate these effects. Additionally, we investigated potential medications by repurposing the molecular links using the DGIdb database, revealing Tacrolimus and Calcitonin as promising candidates, particularly since they possess binding sites on the SPP1 molecule. In conclusion, our study unveils crucial molecular bridges between metabolic syndrome and AD, providing insights into their pathophysiology for therapeutic interventions.<\/jats:p>","DOI":"10.1371\/journal.pone.0304410","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T17:37:41Z","timestamp":1717004261000},"page":"e0304410","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer\u2019s disease through a systems biology approach and drug repurposing"],"prefix":"10.1371","volume":"19","author":[{"given":"Zahra","family":"Azizan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2770-5759","authenticated-orcid":true,"given":"Hakimeh","family":"Zali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Amir","family":"Mirmotalebisohi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Bazrgar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6668-2302","authenticated-orcid":true,"given":"Abolhassan","family":"Ahmadiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,29]]},"reference":[{"key":"pone.0304410.ref001","first-page":"70","article-title":"Western diet as a trigger of Alzheimer\u2019s disease: From metabolic syndrome and systemic inflammation to neuroinflammation and neurodegeneration.","author":"A Wi\u0119ckowska-Gacek","year":"2021","journal-title":"Ageing Res Rev"},{"issue":"1","key":"pone.0304410.ref002","first-page":"63","article-title":"The global prevalence of dementia: A systematic review and metaanalysis. 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