Integrated Bioinformatics Analysis to Identify Alternative Therapeutic Targets for Alzheimer’s Disease: Insights from a Synaptic Machinery Perspective

• Published in: Journal of molecular neuroscience Vol. 72; no. 2; pp. 273 - 286
• Main Author: Ceylan, Hamid
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2022; Springer Nature B.V
• Subjects: Alzheimer's disease; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cell Biology; Datasets; Dementia disorders; Gene expression; Genes; miRNA; Molecular modelling; Neurochemistry; Neurodegenerative diseases; Neurology; Neurosciences; Pathogenesis; Proteomics; Signs and symptoms; SNAP-25 protein; Therapeutic targets; miRNA; Differentially expressed genes; mRNA; Integrated analysis; Alzheimer's disease
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-021-01893-9

Alzheimer's disease (AD), the most common type of dementia, is a serious neurodegenerative disease that has no cure yet, but whose symptoms can be alleviated with available medications. Therefore, early and accurate diagnosis of the disease and elucidation of the molecular mechanisms involved in the progression of pathogenesis are critically important. This study aimed to identify dysregulated miRNAs and their target mRNAs through the integrated analysis of miRNA and mRNA expression profiling in AD patients versus unaffected controls. Expression profiles in postmortem brain samples from AD patients and healthy individuals were extracted from the Gene Expression Omnibus database and were analyzed using bioinformatics approaches to identify gene ontologies, pathways, and networks. Finally, the module analysis of the PPI network and hub gene selection was carried out. A total of five differentially expressed miRNAs were extracted from the miRNA dataset, and 4312 differentially expressed mRNAs were obtained from the mRNA dataset. By comparing the DEGs and the putative targets of the altered miRNAs, 116 (3 upregulated and 113 downregulated) coordinated genes were determined. Also, six hub genes ( SNAP25, GRIN2A, GRIN2B, DLG2, ATP2B2 , and SCN2A ) were identified by constructing a PPI network. The results of the present study provide insight into mechanisms such as synaptic machinery and neuronal communication underlying AD pathogenesis, specifically concerning miRNAs.