The analysis of the differentially expressed Genes in entorhinal cortex and hippocampus for Alzheimer's disease

[Speaker] Ailin Liu:1
[Co-author] Xiaocong Pang:1, Ying Zhao:1, Lvjie Xu:1, Guanhua Du:1
1:Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, China

Alzheimer's disease (AD) is one complicated disease, its pathological mechanisms has not been elucidated. This study aimed to find out the pathogenesis of learning and memory impairment, potential therapeutic targets and drugs for AD.
In this study, we downloaded the microarray data of entorhinal cortex (EC) and hippocampus (HIP) of AD and controls from Gene Expression Omnibus (GEO) database, and then the differentially expressed genes (DEGs) in EC and HIP regions were analyzed for functional and pathway enrichment analysis to elucidate the pathological mechanism of AD in EC and HIP regions. Furthermore, we utilized the DEGs in EC and HIP to construct co-expression networks to identify hub genes, and the top 500 DEGs were uploaded to the Connectivity Map (CMAP) database to discover the connection of disease-gene-drug and the small molecules which were capable of reversing the gene expression profile of AD.
As a result, we found some functional hub genes, and the encoding proteins of them related with AD treatment, such as ErbB2, ErbB4, OCT3, MIF, CDK13 and GPI. According to GO_BP and KEGG pathway enrichment by DAVID and GSEA, several pathways were significantly dysregulated in EC and HIP, such as PI3K-Akt signaling pathway, MAPK signaling pathway, insulin signaling pathway, oxidative phosphorylation, synaptic vesicle cycle, cell-cell adhesion, proteasome, arginine and proline metabolism, pentose phosphate pathway, calcium ion regulated exocytosis, and glutamate receptor signaling pathway. Based on the down-regulated and up-regulated genes, eight small molecules, which may be used for treatment of AD, were screened out.
In conclusion, these biological pathways and DEGs or hub genes will be useful to elucidate AD pathogenesis and identify drug targets for developing therapeutics against AD.

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