{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T19:27:13Z","timestamp":1771615633359,"version":"3.50.1"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL), often recognized as Nasu-Hakola disease, is an uncommon autosomal recessive systemic condition described by numerous bone lesions that resemble cysts and progressive early-onset dementia. One novel way to find possible drug targets is to use Network Analyst tools for network-based gene expression profiling. Identifying the target hub genes, essential for the initiation and progression of PLOSL, is validated by the significance level (p-score) attained using Cytoscape in the survival analysis of the major central genes. The X2K online tool also examined the regulatory kinases that formed the interaction between protein molecule networks. Out of the 53 genes obtained to be differentially expressed, PPARG and AIF1 had the greatest degree score, followed by C1QA with 5 degrees and SIGLEC1 and MSR1 with 4 degrees. Furthermore, Molecular docking of target PPARG gene with AMG-131 and Elafibranor drugs, having the chemical formulas 2-[2,6-dimethyl-4-[(E)-3-(4-methylsulfanylphenyl)-3-oxoprop-1-enyl]phenoxy], and 3,5-dichloro-4-quinolin-3-yloxyphenyl) benzenesulfonamide, along control (Rosiglitazone (S) shows binding affinities of \u22127.2 kcal\/mol, \u22127.4 kcal\/mol, and \u22127.6 kcal\/mol respectively. The enzyme remained extremely stable in the complex throughout 200 ns, with a mean Root Mean Square Deviation (RMSD) of 2.95 \u00c5 for the AMG-131 complex system and 2.93 \u00c5 against the Elafibranor complex system. Root Mean Square Fluctuation (RMSF) anticipated steady behavior with average RMSD for the active site residues in the docked system. Arg76 and Leu28leu Leu118 were shown to be essential enzyme residues for binding, anchoring, and bridging strong hydrogen and hydrophobic interactions between the enzyme and the inhibitor, according to the Radial Distribution Function (RDF). These results broadened our knowledge of putative biomarkers for PLOSL diseases, and an experimental strategy will improve our results even more in the future.<\/jats:p>","DOI":"10.1371\/journal.pone.0343274","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:45:51Z","timestamp":1771613151000},"page":"e0343274","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["System biology and network-based approach to identify the therapeutic signatures and potential inhibitors against polycystic lipomembranous osteodysplasia with Sclerosing Leukoencephalopathy"],"prefix":"10.1371","volume":"21","author":[{"given":"Bayan T.","family":"Bokhari","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaa M.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hashim M.","family":"Aljohani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wejdan Hussain","family":"Owaydhah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6911-9179","authenticated-orcid":true,"given":"Mohammad Ahmad","family":"Alobaidy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3560-8166","authenticated-orcid":true,"given":"Naief","family":"Dahran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hind M.","family":"Naffadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8973-5948","authenticated-orcid":true,"given":"Alaa Abdulaziz","family":"Eisa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"pone.0343274.ref001","article-title":"Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy","volume-title":"GeneReviews\u00ae","author":"MP Adam","year":"1993"},{"issue":"21","key":"pone.0343274.ref002","first-page":"2520","article-title":"Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy","volume":"120","author":"H Schrader","year":"2000","journal-title":"Tidsskr Nor Laegeforen"},{"key":"pone.0343274.ref003","first-page":"89","article-title":"The TREM2-DAP12 signaling pathway in Nasu-Hakola disease: a molecular genetics perspective","volume":"5","author":"J Xing","year":"2015","journal-title":"Res Rep Biochem"},{"issue":"3","key":"pone.0343274.ref004","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1086\/342259","article-title":"Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype","volume":"71","author":"J Paloneva","year":"2002","journal-title":"Am J Hum Genet"},{"issue":"5","key":"pone.0343274.ref005","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.5114\/aoms\/169476","article-title":"A mild type of Nasu-Hakola disease - 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