Investigating the energy crisis in Alzheimer disease using transcriptome study
Investigating the energy crisis in Alzheimer disease using transcriptome study
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DOI：
10.1038/s41598-019-54782-y
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发表时间：
2019-12-06
影响因子：
4.6
通讯作者：
Gromiha, M. Michael
中科院分区：
文献类型：
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作者：
Dharshini, S. Akila P. Arvathy;Taguchi, Y-h.;Gromiha, M. Michael
阿尔茨海默病（AD）是一种毁灭性的神经系统疾病，从海马体开始扩散到皮质区域。海马体的神经元需要更高的能量来保持放电模式。在AD中，能量代谢异常是神经退行性变的关键因素。然而，海马神经元能量危机的原因仍未解决。转录组分析使我们能够了解能源危机的根本机制。在这项研究中，我们从海马 RNA-seq 数据中鉴定了变异/差异基因/转录本表达谱。我们使用计算机工具预测了转录因子 (TF) 结合中变异的影响。此外，设计了海马特异性共表达和功能相互作用网络来破译 TF 和差异表达基因 (DG) 之间的关系。已识别的变体主要影响 TF 结合，随后调节 DG。根据结果，我们假设血管完整性的丧失是能量危机的基本属性，从而导致神经退行性变。
Alzheimer disease (AD) is a devastating neurological disorder, which initiates from hippocampus and proliferates to cortical regions. The neurons of hippocampus require higher energy to preserve the firing pattern. In AD, aberrant energy metabolism is the critical factor for neurodegeneration. However, the reason for the energy crisis in hippocampus neurons is still unresolved. Transcriptome analysis enables us in understanding the underlying mechanism of energy crisis. In this study, we identified variants/differential gene/transcript expression profiles from hippocampus RNA-seq data. We predicted the effect of variants in transcription factor (TF) binding using in silico tools. Further, a hippocampus-specific co-expression and functional interaction network were designed to decipher the relationships between TF and differentially expressed genes (DG). Identified variants predominantly influence TF binding, which subsequently regulates the DG. From the results, we hypothesize that the loss of vascular integrity is the fundamental attribute for the energy crisis, which leads to neurodegeneration.