Identification of molecular signatures and pathways to identify novel therapeutic targets in Alzheimer's disease: Insights from a systems biomedicine perspective

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dc.authoridHolsinger, R. M. Damian/0000-0002-4447-0835
dc.authoridIslam, Tania/0000-0002-2254-7758
dc.authoridMoni, Mohammad Ali/0000-0003-0756-1006
dc.contributor.authorRahman, Md Rezanur
dc.contributor.authorIslam, Tania
dc.contributor.authorZaman, Toyfiquz
dc.contributor.authorShahjaman, Md
dc.contributor.authorKarim, Md Rezaul
dc.contributor.authorHuq, Fazlul
dc.contributor.authorQuinn, Julian M. W.
dc.date.accessioned2025-01-06T17:44:34Z
dc.date.available2025-01-06T17:44:34Z
dc.date.issued2020
dc.description.abstractAlzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. However, there are no peripheral biomarkers available that can detect AD onset. This study aimed to identify the molecular signatures in AD through an integrative analysis of blood gene expression data. We used two microarray datasets (GSE4226 and GSE4229) comparing peripheral blood transcriptomes of AD patients and controls to identify differentially expressed genes (DEGs). Gene set and protein overrepresentation analysis, protein-protein interaction (PPI), DEGs-Transcription Factors (TFs) interactions, DEGs-microRNAs (miRNAs) interactions, protein-drug interactions, and protein subcellular localizations analyses were performed on DEGs common to the datasets. We identified 25 common DEGs between the two datasets. Integration of genome scale transcriptome datasets with biomolecular networks revealed hub genes (NOL6, ATF3, TUBB, UQCRC1, CASP2, SND1, VCAM1, BTF3, VPS37B), common transcription factors (FOXC1, GATA2, NFIC, PPARG, USF2, YY1) and miRNAs (mir-20a-5p, mir-93-5p, mir-16-5p, let-7b-5p, mir-7085p, mir-24-3p, mir-26b-5p, mir-17-5p, mir-193-3p, mir-186-5p). Evaluation of histone modifications revealed that hub genes possess several histone modification sites associated with AD. Protein-drug interactions revealed 10 compounds that affect the identified AD candidate biomolecules, including anti-neoplastic agents (Vinorelbine, Vincristine, Vinblastine, Epothilone D, Epothilone B, CYT997, and ZEN-012), a dermatological (Podofilox) and an immunosuppressive agent (Colchicine). The subcellular localization of molecular signatures varied, including nuclear, plasma membrane and cytosolic proteins. In the present study, it was identified blood-cell derived molecular signatures that might be useful as candidate peripheral biomarkers in AD. It was also identified potential drugs and epigenetic data associated with these molecules that may be useful in designing therapeutic approaches to ameliorate AD.
dc.identifier.doi10.1016/j.ygeno.2019.07.018
dc.identifier.endpage1299
dc.identifier.issn0888-7543
dc.identifier.issn1089-8646
dc.identifier.issue2
dc.identifier.pmid31377428
dc.identifier.scopus2-s2.0-85070841283
dc.identifier.scopusqualityQ1
dc.identifier.startpage1290
dc.identifier.urihttps://doi.org/10.1016/j.ygeno.2019.07.018
dc.identifier.urihttps://hdl.handle.net/20.500.14669/3092
dc.identifier.volume112
dc.identifier.wosWOS:000514071600027
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofGenomics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241211
dc.subjectSystems biology
dc.subjectProtein subcellular localization
dc.subjectEpigenetics
dc.subjectProtein-drug interaction
dc.subjectProtein-protein interaction
dc.titleIdentification of molecular signatures and pathways to identify novel therapeutic targets in Alzheimer's disease: Insights from a systems biomedicine perspective
dc.typeArticle

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