| 苏 燕,朱蓓蓓,王子沫,陈 欣,顾小萍.阿尔茨海默病患者海马中与学习记忆相关的枢纽基因鉴定及机制分析[J].,2025,(1):174-183 |
| 阿尔茨海默病患者海马中与学习记忆相关的枢纽基因鉴定及机制分析 |
| Identification and Mechanism Analysis of Learning and Memory Related Hub Genes in the Hippocampus of Alzheimer's Disease |
| 投稿时间：2024-10-28 |
| DOI：10.13241/j.cnki.pmb.2025.01.025 |
| 中文关键词: 阿尔茨海默病 学习与记忆 生物信息学分析 枢纽基因 |
| 英文关键词: Alzheimer's disease Learning and memory Bioinformatics analysis Hub genes |
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| 中文摘要: |
| 摘要 目的：阿尔茨海默病（Alzheimer's Disease，AD）是一种以学习和记忆能力逐渐下降为显著特征的神经退行性疾病，我们通过生物信息学分析识别其相关枢纽基因，以探索潜在的靶向治疗方法。方法：本研究从Gene Expression Omnibus（GEO）数据库中提取了AD患者的基因表达数据，包括GSE5281和GSE36980，并通过GSEA数据库检索了学习与记忆相关的基因集。在GSE5281与GSE36980差异表达基因的重叠部分，我们共鉴定出158个与海马区AD相关的基因。这些基因随后被用于基因本体论（Gene Ontology, GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）途径富集分析，进而构建了蛋白-蛋白相互作用（Protein-Protein Interaction, PPI）网络。在识别出PPI网络中的20个枢纽基因后，我们再次进行GO和KEGG通路的富集分析，最终鉴定出3个关键的学习与记忆基因。结果：本研究发现，PPI网络中的20个枢纽基因在GO和KEGG通路的突触变化中显著富集，提示这些基因可能在突触功能的调控中发挥重要作用。此外，这些基因的富集分析结果与158个AD相关基因的分析结果呈现出相似的趋势，进一步支持其在AD病理机制中的潜在关键作用。随后，我们通过深入分析PPI网络中最为紧密连接的20个枢纽基因，结合MCODE和cytoHubba的分析结果，最终筛选并确定了3个与学习和记忆密切相关的核心枢纽基因（SNAP25、SYT4和GABRG2）。结论：SNAP25、SYT4 和 GABRG2 可能作为AD的生物标志物和治疗靶点，为改善学习与记忆能力的逐渐下降提供了新的治疗思路。 |
| 英文摘要: |
| ABSTRACT Objective: Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in learning and memory abilities. Using bioinformatics analysis, we aim to identify its related hub genes to explore potential targeted therapeutic strategies. Methods: The study extracted gene expression data from AD patients from the Gene Expression Omnibus (GEO) database, including GSE5281 and GSE36980, and retrieved learning and memory-related gene sets through the GSEA database. From the overlapping differentially expressed genes in GSE5281 and GSE36980, we identified a total of 158 genes associated with the hippocampus in AD. These genes were then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, leading to the construction of a Protein-Protein Interaction (PPI) network. After identifying 20 hub genes in the PPI network, we conducted further GO and KEGG pathway enrichment analyses, ultimately identifying three key genes related to learning and memory. Results: This study found that the 20 hub genes in the PPI network were significantly enriched in synaptic changes within GO and KEGG pathways, suggesting their critical role in regulating synaptic function. Additionally, the enrichment analysis results of these genes showed a similar trend to those of 158 AD-related genes, further supporting their potential key roles in the pathological mechanisms of AD. Subsequently, through an in-depth analysis of the 20 most tightly connected hub genes in the PPI network, combined with results from MCODE and cytoHubba, we ultimately identified three core hub genes-SNAP25, SYT4, and GABRG2-closely associated with learning and memory. Conclusion: SNAP25, SYT4, and GABRG2 may serve as biomarkers and therapeutic targets for AD, offering new strategies for improving the progressive decline in learning and memory abilities. |
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