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Integrated Bioinformatics Analysis to Identify Alternative Therapeutic Targets for Alzheimer’s Disease: Insights from a Synaptic Machinery Perspective
Journal of Molecular Neuroscience ( IF 3.1 ) Pub Date : 2021-08-19 , DOI: 10.1007/s12031-021-01893-9
Hamid Ceylan 1
Affiliation  

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.



中文翻译:

综合生物信息学分析以确定阿尔茨海默病的替代治疗靶点:从突触机械角度的见解

阿尔茨海默病 (AD) 是最常见的痴呆类型,是一种严重的神经退行性疾病,目前尚无治愈方法,但可用药物缓解其症状。因此,对疾病的早期和准确诊断以及阐明参与发病机制进展的分子机制至关重要。本研究旨在通过综合分析 AD 患者与未受影响的对照中的 miRNA 和 mRNA 表达谱来识别失调的 miRNA 及其靶 mRNA。从基因表达综合数据库中提取 AD 患者和健康个体的死后脑样本中的表达谱,并使用生物信息学方法进行分析,以识别基因本体、通路和网络。最后,进行了PPI网络和hub基因选择的模块分析。从miRNA数据集中提取了5个差异表达的miRNA,从mRNA数据集中获得了4312个差异表达的mRNA。通过比较 DEG 和改变的 miRNA 的推定目标,确定了 116 个(3 个上调和 113 个下调)协调基因。此外,六个中心基因(SNAP25、GRIN2A、GRIN2B、DLG2、ATP2B2SCN2A)通过构建 PPI 网络进行识别。本研究的结果提供了深入了解 AD 发病机制的机制,如突触机制和神经元通讯,特别是关于 miRNA。

更新日期:2021-08-20
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