State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Beijing Key Laboratory of Drug Target and Screening Research, Beijing 100050, China.
Biomed Res Int. 2017;2017:9084507. doi: 10.1155/2017/9084507. Epub 2017 Nov 21.
The incidence of Alzheimer's disease (AD) has been increasing in recent years, but there exists no cure and the pathological mechanisms are not fully understood. This study aimed to find out the pathogenesis of learning and memory impairment, new biomarkers, potential therapeutic targets, and drugs for AD.
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. Furthermore, we utilized the DEGs to construct coexpression networks to identify hub genes and discover the small molecules which were capable of reversing the gene expression profile of AD. Finally, we also analyzed microarray and RNA-seq dataset of blood samples to find the biomarkers related to gene expression in brain.
We found some functional hub genes, such as , , , , , and . According to GO and KEGG pathway enrichment, several pathways were significantly dysregulated in EC and HIP. and were dysregulated significantly in blood, EC, and HIP, which were potential biomarkers for AD. Target genes of four microRNAs had similar GO_terms distribution with DEGs in EC and HIP. In addtion, small molecules were screened out for AD treatment.
These biological pathways and DEGs or hub genes will be useful to elucidate AD pathogenesis and identify novel biomarkers or drug targets for developing improved diagnostics and therapeutics against AD.
近年来,阿尔茨海默病(AD)的发病率一直在上升,但目前尚无治愈方法,其病理机制也不完全清楚。本研究旨在探讨学习和记忆障碍的发病机制、新的生物标志物、潜在的治疗靶点和 AD 的药物。
我们从基因表达综合数据库(GEO)下载了 AD 和对照的内嗅皮层(EC)和海马(HIP)的微阵列数据,然后对 EC 和 HIP 区域的差异表达基因(DEGs)进行功能和通路富集分析。此外,我们利用 DEGs 构建共表达网络,以识别关键基因,并发现能够逆转 AD 基因表达谱的小分子。最后,我们还分析了血液样本的微阵列和 RNA-seq 数据集,以寻找与大脑基因表达相关的生物标志物。
我们发现了一些功能关键基因,如、、、、、和。根据 GO 和 KEGG 通路富集分析,EC 和 HIP 中几个通路明显失调。和在血液、EC 和 HIP 中显著失调,是 AD 的潜在生物标志物。四个 microRNAs 的靶基因与 EC 和 HIP 中的 DEGs 具有相似的 GO_terms 分布。此外,还筛选出了用于 AD 治疗的小分子。
这些生物学途径和 DEGs 或关键基因将有助于阐明 AD 的发病机制,并为开发改善 AD 的诊断和治疗的新生物标志物或药物靶点提供有用信息。