Linking Diabetes Mellitus with Alzheimer's Disease: Bioinformatics Analysis for the Potential Pathways and Characteristic Genes
Linking Diabetes Mellitus with Alzheimer's Disease: Bioinformatics Analysis for the Potential Pathways and Characteristic Genes
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DOI：
10.1007/s10528-021-10154-8
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发表时间：
2021-11-15
影响因子：
2.4
通讯作者：
Li, Keshen
中科院分区：
文献类型：
--
作者：
Huang, Cheng;Luo, Juyu;Li, Keshen
阿尔茨海默病（Alzheimer's disease， AD）与伴有微血管并发症的2型糖尿病（type 2 diabetes mellitus, T2DM）作为一种日益流行的重大致残疾病，普遍存在，在推测的发病机制上有相当大的相似性。尽管在生物学方面的研究突飞猛进，但关于它们相互作用机制的知识仍然是初级的。应用生物信息学方法探索差异共表达基因有助于实现我们寻找新的治疗靶点的目标。在本研究中，我们首先整合基因表达综合数据集（GSE28146和GSE43950）来鉴定差异表达基因。随后进行了关键基因的富集分析，如基因本体和通路信号。此外，构建了相关蛋白-蛋白相互作用（PPI）网络。为了进一步解释内在联系，我们最终发现了有价值靶点的生物学意义。结果，在T2DM微血管并发症和早期、中度和重度AD中分别鉴定出712、630、487和997组基因。两种疾病的富集分析都暗示了免疫系统的优势，特别是值得注意的趋化因子信号。多重比较证实CACNA2D3、NUMB和IER3同时参与了这两种疾病，并分析了它们各自与神经和内分泌疾病的关联，以及相互作用化学物质、转录因子和mirna等调节因子。生物信息学分析最终得出免疫相关的生物学功能和途径与AD和T2DM微血管并发症密切相关。进一步探索CACNA2D3、NUMB和IER3在神经内分泌领域的调控因子，可能为我们发现合并症的潜在策略提供一个有希望的方向。
As the surging epidemics with significant disability, Alzheimer's disease (AD) and type II diabetes mellitus (T2DM) with microvascular complications are widely prevalent, sharing considerable similarities in putative pathomechanism. Despite a spurt of researches on the biology, knowledge about their interactive mechanisms is still rudimentary. Applying bioinformatics ways to explore the differentially co-expressed genes contributes to achieve our objectives to find new therapeutic targets. In this study, we firstly integrated gene expression omnibus datasets (GSE28146 and GSE43950) to identify differentially expressed genes. The enrichment analysis of pivotal genes, like gene ontology and pathway signaling proceeded subsequently. Besides, the related protein-protein interaction (PPI) network was then constructed. To further explain the inner connections, we ended up unearthing the biological significance of valuable targets. As a result, a set of 712, 630, 487, and 997 genes were differentially identified in T2DM with microvascular complications and AD at incipient, moderate, and severe, respectively. The enrichment analysis involving both diseases implicated the dominance of immune system, especially the noteworthy chemokine signaling. Multiple comparisons confirmed that CACNA2D3, NUMB, and IER3 were simultaneously participate in these two conditions, whose respective associations with neurological and endocrine diseases, and regulators including interacting chemicals, transcription factors, and miRNAs were analyzed. Bioinformatics analysis eventually concluded that immune-related biological functions and pathways closely link AD and T2DM with microvascular complications. Further exploration of the regulatory factors about CACNA2D3, NUMB, and IER3 in neuroendocrine field may provide us a promising direction to discover potential strategies for the comorbidity status.