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Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways

OBJECTIVE: The inability to intervene in Alzheimer's disease (AD) forces the search for promising gene-targeted therapies. This study was aimed at exploring molecular signatures and mechanistic pathways to improve the diagnosis and treatment of AD. METHODS: Microarray datasets were collected to...

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Autores principales: Chen, Fenqin, Bai, Jun, Zhong, Shanshan, Zhang, Rongwei, Zhang, Xiaoqian, Xu, Ying, Zhao, Mei, Zhao, Chuansheng, Zhou, Zhike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006080/
https://www.ncbi.nlm.nih.gov/pubmed/35432724
http://dx.doi.org/10.1155/2022/9565545
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author Chen, Fenqin
Bai, Jun
Zhong, Shanshan
Zhang, Rongwei
Zhang, Xiaoqian
Xu, Ying
Zhao, Mei
Zhao, Chuansheng
Zhou, Zhike
author_facet Chen, Fenqin
Bai, Jun
Zhong, Shanshan
Zhang, Rongwei
Zhang, Xiaoqian
Xu, Ying
Zhao, Mei
Zhao, Chuansheng
Zhou, Zhike
author_sort Chen, Fenqin
collection PubMed
description OBJECTIVE: The inability to intervene in Alzheimer's disease (AD) forces the search for promising gene-targeted therapies. This study was aimed at exploring molecular signatures and mechanistic pathways to improve the diagnosis and treatment of AD. METHODS: Microarray datasets were collected to filter differentially expressed genes (DEGs) between AD and nondementia controls. Weight gene correlation network analysis (WGCNA) was employed to analyze the correlation of coexpression modules with AD phenotype. A global regulatory network was established and then visualized using Cytoscape software to determine hub genes and their mechanistic pathways. Receiver operating characteristic (ROC) analysis was conducted to estimate the diagnostic performance of hub genes in AD prediction. RESULTS: A total of 2,163 DEGs from 13,049 background genes were screened in AD relative to nondementia controls. Among the six coexpression modules constructed by WGCNA, DEGs of the key modules with the strongest correlation with AD were extracted to build a global regulatory network. According to the Maximal Clique Centrality (MCC) method, five hub genes associated with mitochondrial complexes were chosen. Further pathway enrichment analysis of hub genes, such as oxidative phosphorylation and retrograde endocannabinoid signaling, was identified. According to the area under the curve (AUC) of about 70%, each hub gene exhibited a good diagnostic performance in predicting AD. CONCLUSIONS: Our findings highlight the perturbation of mitochondrial complexes underlying AD onset, which is mediated by molecular signatures involved in oxidative phosphorylation (COX5A, NDUFAB1, SDHB, UQCRC2, and UQCRFS1) and retrograde endocannabinoid signaling (NDUFAB1) pathways.
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spelling pubmed-90060802022-04-14 Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways Chen, Fenqin Bai, Jun Zhong, Shanshan Zhang, Rongwei Zhang, Xiaoqian Xu, Ying Zhao, Mei Zhao, Chuansheng Zhou, Zhike Oxid Med Cell Longev Research Article OBJECTIVE: The inability to intervene in Alzheimer's disease (AD) forces the search for promising gene-targeted therapies. This study was aimed at exploring molecular signatures and mechanistic pathways to improve the diagnosis and treatment of AD. METHODS: Microarray datasets were collected to filter differentially expressed genes (DEGs) between AD and nondementia controls. Weight gene correlation network analysis (WGCNA) was employed to analyze the correlation of coexpression modules with AD phenotype. A global regulatory network was established and then visualized using Cytoscape software to determine hub genes and their mechanistic pathways. Receiver operating characteristic (ROC) analysis was conducted to estimate the diagnostic performance of hub genes in AD prediction. RESULTS: A total of 2,163 DEGs from 13,049 background genes were screened in AD relative to nondementia controls. Among the six coexpression modules constructed by WGCNA, DEGs of the key modules with the strongest correlation with AD were extracted to build a global regulatory network. According to the Maximal Clique Centrality (MCC) method, five hub genes associated with mitochondrial complexes were chosen. Further pathway enrichment analysis of hub genes, such as oxidative phosphorylation and retrograde endocannabinoid signaling, was identified. According to the area under the curve (AUC) of about 70%, each hub gene exhibited a good diagnostic performance in predicting AD. CONCLUSIONS: Our findings highlight the perturbation of mitochondrial complexes underlying AD onset, which is mediated by molecular signatures involved in oxidative phosphorylation (COX5A, NDUFAB1, SDHB, UQCRC2, and UQCRFS1) and retrograde endocannabinoid signaling (NDUFAB1) pathways. Hindawi 2022-04-05 /pmc/articles/PMC9006080/ /pubmed/35432724 http://dx.doi.org/10.1155/2022/9565545 Text en Copyright © 2022 Fenqin Chen et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Fenqin
Bai, Jun
Zhong, Shanshan
Zhang, Rongwei
Zhang, Xiaoqian
Xu, Ying
Zhao, Mei
Zhao, Chuansheng
Zhou, Zhike
Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways
title Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways
title_full Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways
title_fullStr Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways
title_full_unstemmed Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways
title_short Molecular Signatures of Mitochondrial Complexes Involved in Alzheimer's Disease via Oxidative Phosphorylation and Retrograde Endocannabinoid Signaling Pathways
title_sort molecular signatures of mitochondrial complexes involved in alzheimer's disease via oxidative phosphorylation and retrograde endocannabinoid signaling pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006080/
https://www.ncbi.nlm.nih.gov/pubmed/35432724
http://dx.doi.org/10.1155/2022/9565545
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