School of Advanced Materials Engineering, Jiaxing Nanhu University, Jiaxing 314001, China.
Genes (Basel). 2024 Aug 5;15(8):1027. doi: 10.3390/genes15081027.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Its accurate pathogenic mechanisms are incompletely clarified, and effective therapeutic treatments are still inadequate. Autophagy is closely associated with AD and plays multiple roles in eliminating harmful aggregated proteins and maintaining cell homeostasis. This study identified 1191 differentially expressed genes (DEGs) based on the GSE5281 dataset from the GEO database, intersected them with 325 autophagy-related genes from GeneCards, and screened 26 differentially expressed autophagy-related genes (DEAGs). Subsequently, GO and KEGG enrichment analysis was performed and indicated that these DEAGs were primarily involved in autophagy-lysosomal biological process. Further, eight hub genes were determined by PPI construction, and experimental validation was performed by qRT-PCR on a SH-SY5Y cell model. Finally, three hub genes (, , ) were confirmed to have potential application for biomarkers. A multigenic prediction model with good predictability (AUC = 0.871) was constructed in GSE5281 and validated in the GSE132903 dataset. Hub gene-targeted miRNAs closely associated with AD were also retrieved through the miRDB and HDMM database, predicting potential therapeutic agents for AD. This study provides new insights into autophagy-related genes in brain tissues of AD patients and offers more candidate biomarkers for AD mechanistic research as well as clinical diagnosis.
阿尔茨海默病（AD）是最常见的神经退行性疾病。其确切的发病机制尚未完全阐明，有效的治疗方法仍然不足。自噬与 AD 密切相关，在清除有害聚集蛋白和维持细胞内稳态方面发挥着多种作用。本研究基于 GEO 数据库中的 GSE5281 数据集，鉴定了 1191 个差异表达基因（DEGs），与 GeneCards 中的 325 个自噬相关基因进行交集，并筛选出 26 个差异表达的自噬相关基因（DEAGs）。随后进行了 GO 和 KEGG 富集分析，结果表明这些 DEAGs 主要参与自噬-溶酶体生物过程。进一步通过 PPI 构建确定了 8 个枢纽基因，并在 SH-SY5Y 细胞模型上通过 qRT-PCR 进行了实验验证。最后，确定了三个具有潜在应用价值的生物标志物候选基因（、、）。在 GSE5281 中构建了一个具有良好预测能力（AUC=0.871）的多基因预测模型，并在 GSE132903 数据集进行了验证。还通过 miRDB 和 HDMM 数据库检索了与 AD 密切相关的枢纽基因靶向 miRNA，预测了 AD 的潜在治疗药物。本研究为 AD 患者脑组织中的自噬相关基因提供了新的见解，并为 AD 机制研究和临床诊断提供了更多的候选生物标志物。
