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阿尔茨海默病患者海马中与原发性纤毛运动障碍相关的关键基因网络通过加权基因共表达网络分析揭示。

Key gene network related to primary ciliary dyskinesia in hippocampus of patients with Alzheimer's disease revealed by weighted gene co-expression network analysis.

机构信息

Department of Clinical Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Discipline of Anatomy and Pathology, Shandong First Medical University, Jinan, Shandong, China.

出版信息

BMC Neurol. 2022 May 30;22(1):198. doi: 10.1186/s12883-022-02724-z.

Abstract

BACKGROUND

Alzheimer's disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main brain regions involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little is known about its association with primary ciliary dyskinesia (PCD).

MATERIAL AND METHODS

The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network.

RESULTS

Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g., DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25, and ARMC4 were identified as hub genes related to PCD in hippocampus of AD patients.

CONCLUSION

Our study demonstrated that AD and PCD have common metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD.

SUBJECTS

Bioinformatics, Cell Biology, Molecular Biology, Neurology.

摘要

背景

阿尔茨海默病(AD)与衰老密切相关,其发病率多年来呈上升趋势。作为 AD 主要涉及的大脑区域之一,由于其与许多人类疾病有关,因此对其进行了广泛研究。然而,关于其与原发性纤毛运动障碍(PCD)的关系知之甚少。

材料和方法

从基因表达综合数据库(GEO)中检索 AD 海马体的微阵列数据,通过加权基因共表达网络分析(WGCNA)构建共表达网络。用共同基因筛选与 AD 相关的基因网络模块,根据基因本体论(GO)数据库进行注释,并根据京都基因与基因组百科全书(KEGG)数据库进行富集。根据 STRING 数据库构建蛋白质-蛋白质相互作用(PPI)网络,以确定网络中的枢纽基因。

结果

在 AD 患者的海马体中鉴定出与 PCD 相关的基因。功能分析表明,这些基因主要富集在纤毛组织、纤毛组装、轴丝组装、纤毛运动、微管为基础的过程、微管为基础的运动、细胞器组装、轴丝动力蛋白复合物、细胞突起组织和微管细胞骨架组织中。共鉴定出 20 个核心基因,如 DYNLRB2、ZMYND10、DRC1、DNAH5、WDR16、TTC25 和 ARMC4,它们是 AD 患者海马体中与 PCD 相关的枢纽基因。

结论

我们的研究表明,AD 和 PCD 有共同的代谢途径。这些共同的途径为进一步研究 AD 和 PCD 的病理生理机制提供了新的证据,而枢纽基因则为 AD 和 PCD 的诊断和治疗提供了新的治疗靶点。

主题

生物信息学、细胞生物学、分子生物学、神经病学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cf6/9150314/bda2837c531d/12883_2022_2724_Fig1_HTML.jpg

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