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对海马体中差异基因表达谱进行综合分析,以鉴定与阿尔茨海默病相关的候选基因。

Integrated analysis of differential gene expression profiles in hippocampi to identify candidate genes involved in Alzheimer's disease.

作者信息

Hu Wanhua, Lin Xiaodong, Chen Kelong

机构信息

Department of Neurology, Wenzhou Hospital of Traditional Chinese Medicine, Wenzhou, Zhejiang 325000, P.R. China.

Department of Traditional Chinese Internal Medicine, Wenzhou Seventh People's Hospital, Wenzhou, Zhejiang 325005, P.R. China.

出版信息

Mol Med Rep. 2015 Nov;12(5):6679-87. doi: 10.3892/mmr.2015.4271. Epub 2015 Aug 28.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. Identifying altered neuronal gene expression in AD may provide diagnostic or therapeutic targets for AD. The present study aimed to identify differentially expressed genes (DEGs) and their further association with other biological processes that regulate causative factors for AD. The present study performed an integrated analysis of publicly available gene expression omnibus datasets of AD hippocampi. Gene ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Protein‑Protein interaction (PPI) network analysis were performed. The present study detected 295 DEGs (109 upregulated and 186 downregulated genes) in hippocampi between AD and control samples by integrating four datasets of gene expression profiles of hippocampi of patients with AD. Respiratory electron transport chain (GO: 0022904; P=1.64x10‑11) was the most significantly enriched GO term among biological processes, while for molecular functions, the most significantly enriched GO term was that of protein binding (GO: 0005515; P=3.03x10‑29), and for cellular components, the most significantly enriched GO term was that of the cytoplasm (GO: 0005737; P=8.67x10‑33). The most significant pathway in the KEGG analysis was oxidative phosphorylation (P=1.61x10‑13). PPI network analysis showed that the significant hub proteins contained β-actin (degree, 268), hepatoma-derived growth factor (degree, 218) and WD repeat‑containing protein 82 (degree, 87). The integrated analysis performed in the present study serves as a basis for identifying novel drug targets to develop improved therapies and interventions for common and devastating neurological diseases such as AD.

摘要

阿尔茨海默病(AD)是一种复杂的神经退行性疾病,其遗传机制在很大程度上尚不明确。识别AD中神经元基因表达的改变可能为AD提供诊断或治疗靶点。本研究旨在识别差异表达基因(DEGs)及其与调节AD致病因素的其他生物学过程的进一步关联。本研究对公开可用的AD海马体基因表达综合数据集进行了综合分析。进行了基因本体论(GO)富集分析、京都基因与基因组百科全书(KEGG)通路分析和蛋白质-蛋白质相互作用(PPI)网络分析。通过整合AD患者海马体基因表达谱的四个数据集,本研究在AD样本与对照样本的海马体中检测到295个DEGs(109个上调基因和186个下调基因)。呼吸电子传递链(GO:0022904;P=1.64×10⁻¹¹)是生物过程中最显著富集的GO术语,而在分子功能方面,最显著富集的GO术语是蛋白质结合(GO:0005515;P=3.03×10⁻²⁹),在细胞成分方面,最显著富集的GO术语是细胞质(GO:0005737;P=8.67×10⁻³³)。KEGG分析中最显著的通路是氧化磷酸化(P=1.61×10⁻¹³)。PPI网络分析表明,显著的枢纽蛋白包括β-肌动蛋白(度数,268)、肝癌衍生生长因子(度数,218)和含WD重复蛋白82(度数,87)。本研究进行的综合分析为识别新的药物靶点提供了基础,以开发针对AD等常见且具有破坏性的神经疾病的改进疗法和干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3690/4626122/55a8d30b3ead/MMR-12-05-6679-g00.jpg

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