摘要
目的使用生物信息学数据处理方法,初步探讨阿尔茨海默病(AD)潜在的分子机制。方法通过GEO2R筛选GSE5281和GSE132903数据集中的差异表达基因(DEGs),利用Metascape、STRING和Cytoscape软件对DEGs进行系统的生物信息学分析,并通过qPCR方法在AD模型小鼠中对筛选到的关键基因进行验证。结果在2个数据集中共筛选出250个重叠的DEGs,主要富集于突触传递、神经系统等条目。通过构建蛋白-蛋白作用网络(PPI),筛选关键基因并验证,最终选出4个关键基因,分别为突触相关蛋白25(SNAP25)、突触蛋白Ⅰ(SYN1)、γ-氨基丁酸A型受体γ2亚基(GABRG2)、突触结合蛋白Ⅳ(SYT4)。结论AD的发病与SNAP25、SYN1、GABRG2、SYT4基因密切相关,主要涉及突触神经递质释放过程。这些发现将有助于深入了解AD发病的分子机制,为未来新药物开发提供潜在的作用靶点,为疾病早期诊断及治疗提供新思路。
Objective To preliminarily explore the potential molecular mechanism of Alzheimer disease(AD)using bioinformatics methods.Methods Differentially expression genes(DEGs)in GSE5281 and GSE132903 datasets were identified using GEO2R,and then systematically analyzed using online Matescape,STRING and Cytoscape softwares.The resultant key genes were further validated in AD mice by qPCR.Results A total of 250 overlapping DEGs were obtained from two datasets.The resultant DEGs mainly focused on synaptic transmission and neuronal system.A protein-protein interaction(PPI)network of DEGs was constructed,while four hub genes were identified,including synaptosomal-associated protein 25(SNAP25),synapsin I(SYN1),gamma-aminobutyric acid s receptor subunit gamma 2(GABRG2),and synaptotagmin 4(SYT4).Conclusions The pathogenesis of AD is closely related to SNAP25,SYN1,GABRG2,and SYT4 genes,which are mainly involved in synaptic neurotransmitter release processes.These findings will provide deepened understanding for molecular mechanism of AD,and give new thoughts for developing potential targets for new drugs and early diagnosis and treatment of AD.
作者
许灿坤
刘久煜
郑英伟
牛海晨
杨荣礼
XU Cankun;LIU Jiuyu;ZHENG Yingwei;NIU Haichen;YANG Rongli(The People′s Hospital of Xuecheng District,Zaozhuang,Shandong 277000,China;Key Laboratory of Bioinformatics Encephalopathy,Xuzhou Medical University,Xuzhou,Jiangsu 221004;Department of Geriatrics,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221002)
出处
《徐州医科大学学报》
CAS
2022年第7期484-490,共7页
Journal of Xuzhou Medical University
基金
徐州市科技局创新研发计划(KY14042012)。
关键词
阿尔茨海默病
生物信息学
差异表达基因
化学突触传递
关键基因
Alzheimer disease
bioinformatics
differentially expressed genes
chemical synaptic transmission
hub genes