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ABSTRACT: Background
Alzheimer's disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete.Methods
Gene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cortex regions between AD patients and healthy controls and detected via Morpheus. Functional enrichment analyses, including Gene Ontology (GO) and pathway analyses of DEGs, were performed via Cytoscape and followed by the construction of protein-protein interaction (PPI) network. Hub proteins were screened using the criteria: nodes degree?10 (for hippocampus tissues) and???8 (for entorhinal cortex tissues). Molecular Complex Detection (MCODE) was used to filtrate the important clusters. University of California Santa Cruz (UCSC) and the database of RNA-binding protein specificities (RBPDB) were employed to identify the RNA-binding proteins of the long non-coding RNA (lncRNA).Results
251 & 74 genes were identified as DEGs, which consisted of 56 & 16 up-regulated genes and 195 & 58 down-regulated genes in hippocampus and entorhinal cortex, respectively. Biological analyses demonstrated that the biological processes and pathways related to memory, transmembrane transport, synaptic transmission, neuron survival, drug metabolism, ion homeostasis and signal transduction were enriched in these genes. 11 genes were identified as hub genes in hippocampus and entorhinal cortex, and 3 hub genes were identified as the novel candidates involved in the pathology of AD. Furthermore, 3 lncRNAs were filtrated, whose binding proteins were closely associated with AD.Conclusions
Through GO enrichment analyses, pathway analyses and PPI analyses, we showed a comprehensive interpretation of the pathogenesis of AD at a systematic biology level, and 3 novel candidate genes and 3 lncRNAs were identified as novel and potential candidates participating in the pathology of AD. The results of this study could supply integrated insights for understanding the pathogenic mechanism underlying AD and potential novel therapeutic targets.
SUBMITTER: Yan T
PROVIDER: S-EPMC6636172 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Yan Tingting T Ding Feng F Zhao Yan Y
Hereditas 20190716
<h4>Background</h4>Alzheimer's disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete.<h4>Methods</h4>Gene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cor ...[more]