关键词: AD SPEG high-fiber diet neurodegenerative diseases neurovascular obesity

来  源:   DOI:10.3389/fneur.2022.1026904   PDF(Pubmed)

Abstract:
UNASSIGNED: Through transcriptomic and metabolomic analyses, this study examined the role of high-fiber diet in obesity complicated by diabetes and neurodegenerative symptoms.
UNASSIGNED: The expression matrix of high-fiber-diet-related metabolites, blood methylation profile associated with pre-symptomatic dementia in elderly patients with type 2 diabetes mellitus (T2DM), and high-throughput single-cell sequencing data of hippocampal samples from patients with Alzheimer\'s disease (AD) were retrieved from the Gene Expression Omnibus (GEO) database and through a literature search. Data were analyzed using principal component analysis (PCA) after quality control and data filtering to identify different cell clusters and candidate markers. A protein-protein interaction network was mapped using the STRING database. To further investigate the interaction among high-fiber-diet-related metabolites, methylation-related DEGs related to T2DM, and single-cell marker genes related to AD, AutoDock was used for semi-flexible molecular docking.
UNASSIGNED: Based on GEO database data and previous studies, 24 marker genes associated with high-fiber diet, T2DM, and AD were identified. Top 10 core genes include SYNE1, ANK2, SPEG, PDZD2, KALRN, PTPRM, PTPRK, BIN1, DOCK9, and NPNT, and their functions are primarily related to autophagy. According to molecular docking analysis, acetamidobenzoic acid, the most substantially altered metabolic marker associated with a high-fiber diet, had the strongest binding affinity for SPEG.
UNASSIGNED: By targeting the SPEG protein in the hippocampus, acetamidobenzoic acid, a metabolite associated with high-fiber diet, may improve diabetic and neurodegenerative diseases in obese people.
摘要:
未经证实:通过转录组和代谢组学分析,这项研究探讨了高纤维饮食在肥胖并发糖尿病和神经退行性症状中的作用。
未经证实:高纤维饮食相关代谢物的表达矩阵,老年2型糖尿病(T2DM)患者的血液甲基化与症状前痴呆相关,从基因表达综合(GEO)数据库和文献检索检索阿尔茨海默病(AD)患者海马样本的高通量单细胞测序数据。在质量控制和数据过滤后,使用主成分分析(PCA)分析数据,以鉴定不同的细胞簇和候选标记。使用STRING数据库绘制蛋白质-蛋白质相互作用网络。为了进一步研究高纤维饮食相关代谢物之间的相互作用,甲基化相关DEGs与T2DM相关,和与AD相关的单细胞标记基因,AutoDock用于半柔性分子对接。
UNASSIGNED:基于GEO数据库数据和以前的研究,与高纤维饮食相关的24个标记基因,T2DM,并确定了AD。前10个核心基因包括SYNE1,ANK2,SPEG,PDZD2,KALRN,PTPRM,PTPRK,BIN1、DOCK9和NPNT,它们的功能主要与自噬有关。根据分子对接分析,乙酰氨基苯甲酸,与高纤维饮食相关的最显著改变的代谢指标,对SPEG具有最强的结合亲和力。
未经证实:通过靶向海马中的SPEG蛋白,乙酰氨基苯甲酸,与高纤维饮食相关的代谢产物,可以改善肥胖人群的糖尿病和神经退行性疾病。
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