NDLI: Exploration of key drug target proteins highlighting their related regulatory molecules, functional pathways and drug candidates associated with delirium: evidence from meta-data analyses

Content Provider	Springer Nature : BioMed Central
Author	Mosharaf, Md Parvez Alam, Khorshed Gow, Jeff Mahumud, Rashidul Alam
Abstract	Background Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering and the economic burden for families and carers. Unfortunately, the pathophysiology of delirium is still unknown, which is a major obstacle to therapeutic development. The modern network-based system biology and multi-omics analysis approach has been widely used to recover the key drug target biomolecules and signaling pathways associated with disease pathophysiology. This study aimed to identify the major drug target hub-proteins associated with delirium, their regulatory molecules with functional pathways, and repurposable drug candidates for delirium treatment. Methods We used a comprehensive proteomic seed dataset derived from a systematic literature review and the Comparative Toxicogenomics Database (CTD). An integrated multi-omics network-based bioinformatics approach was utilized in this study. The STRING database was used to construct the protein-protein interaction (PPI) network. The gene set enrichment and signaling pathways analysis, the regulatory transcription factors and microRNAs were conducted using delirium-associated genes. Finally, hub-proteins associated repurposable drugs were retrieved from CMap database. Results We have distinguished 11 drug targeted hub-proteins (MAPK1, MAPK3, TP53, JUN, STAT3, SRC, RELA, AKT1, MAPK14, HSP90AA1 and DLG4), 5 transcription factors (FOXC1, GATA2, YY1, TFAP2A and SREBF1) and 6 microRNA (miR-375, miR-17-5, miR-17-5p, miR-106a-5p, miR-125b-5p, and miR-125a-5p) associated with delirium. The functional enrichment and pathway analysis revealed the cytokines, inflammation, postoperative pain, oxidative stress-associated pathways, developmental biology, shigellosis and cellular senescence which are closely connected with delirium development and the hallmarks of aging. The hub-proteins associated computationally identified repurposable drugs were retrieved from database. The predicted drug molecules including aspirin, irbesartan, ephedrine-(racemic), nedocromil, and guanidine were characterized as anti-inflammatory, stimulating the central nervous system, neuroprotective medication based on the existing literatures. The drug molecules may play an important role for therapeutic development against delirium if they are investigated more extensively through clinical trials and various wet lab experiments. Conclusion This study could possibly help future research on investigating the delirium-associated therapeutic target biomarker hub-proteins and repurposed drug compounds. These results will also aid understanding of the molecular mechanisms that underlie the pathophysiology of delirium onset and molecular function.
Related Links	https://bmcgeriatr.biomedcentral.com/counter/pdf/10.1186/s12877-023-04457-1.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	14712318
DOI	10.1186/s12877-023-04457-1
Journal	BMC Geriatrics
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2023-11-22
Access Restriction	Open
Subject Keyword	Geriatrics Gerontology Aging Rehabilitation Delirium Hub-proteins Transcription factors microRNA Drug repurposing Geriatrics/Gerontology
Content Type	Text
Resource Type	Article
Subject	Geriatrics and Gerontology
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	4.1/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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