Network-based approach to identify molecular signatures and therapeutic agents in Alzheimer's disease. (February 2019)

• Record Type: Journal Article
• Authors: Rahman, Md. Rezanur; Islam, Tania; Turanli, Beste; Zaman, Toyfiquz; Faruquee, Hossain Md.; Rahman, Md. Mafizur; Mollah, Md. Nurul Haque; Nanda, Ranjan Kumar; Arga, Kazim Yalcin; Gov, Esra; Moni, Mohammad Ali
• Is Part Of: Computational biology and chemistry. Volume 78(2019)
• Page Start: 431
• Page End: 439
• Publication Date: 2019-02
• Subjects: Alzheimer's disease -- Network biology -- Differentially expressed genes -- Transcription factors -- microRNAs -- Candidate drugs; Chemistry -- Data processing -- Periodicals; Biology -- Data processing -- Periodicals; Biochemistry -- Data processing; Biology -- Data processing; Molecular biology -- Data processing; Periodicals; Electronic journals; 542.85
• DOI: 10.1016/j.compbiolchem.2018.12.011
• Languages: English
• ISSNs: 1476-9271

Abstract

Abstract: Alzheimer's disease (AD) is a dynamic degeneration of the brain with progressive dementia. Considering the uncertainties in its molecular mechanism, in the present study, we employed network-based integrative analyses, and aimed to explore the key molecules and their associations with small drugs to identify potential biomarkers and therapeutic agents for the AD. First of all, we studied a transcriptome dataset and identified 1521 differentially expressed genes (DEGs). Integration of transcriptome data with protein-protein and transcriptional regulatory interactions resulted with central (hub) proteins (UBA52, RAC1, CREBBP, AR, RPS11, SMAD3, RPS6, RPL12, RPL15, and UBC), regulatory transcription factors (FOXC1, GATA2, YY1, FOXL1, NFIC, E2F1, USF2, SRF, PPARG, and JUN) and microRNAs (mir-335-5p, mir-26b-5p, mir-93-5p, mir-124-3p, mir-17-5p, mir-16-5p, mir-20a-5p, mir-92a-3p, mir-106b-5p, and mir-192-5p) as key signaling and regulatory molecules associated with transcriptional changes for the AD. Considering these key molecules as potential therapeutic targets and Connectivity Map (CMap) architecture, candidate small molecular agents (such as STOCK1N-35696) were identified as novel potential therapeutics for the AD. This study presents molecular signatures at RNA and protein levels which might be useful in increasing discernment of the molecular mechanisms, and potential drug targets and therapeutics to design effective treatment strategies for the AD.