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Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis

The complex pathology of Alzheimer’s disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and in...

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Autores principales: Bayraktar, Abdulahad, Lam, Simon, Altay, Ozlem, Li, Xiangyu, Yuan, Meng, Zhang, Cheng, Arif, Muhammad, Turkez, Hasan, Uhlén, Mathias, Shoaie, Saeed, Mardinoglu, Adil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584243/
https://www.ncbi.nlm.nih.gov/pubmed/34768988
http://dx.doi.org/10.3390/ijms222111556
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author Bayraktar, Abdulahad
Lam, Simon
Altay, Ozlem
Li, Xiangyu
Yuan, Meng
Zhang, Cheng
Arif, Muhammad
Turkez, Hasan
Uhlén, Mathias
Shoaie, Saeed
Mardinoglu, Adil
author_facet Bayraktar, Abdulahad
Lam, Simon
Altay, Ozlem
Li, Xiangyu
Yuan, Meng
Zhang, Cheng
Arif, Muhammad
Turkez, Hasan
Uhlén, Mathias
Shoaie, Saeed
Mardinoglu, Adil
author_sort Bayraktar, Abdulahad
collection PubMed
description The complex pathology of Alzheimer’s disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and individuals with late-onset AD from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MayoRNAseq) studies in the AMP-AD consortium. In this context, we conducted several bioinformatics and systems medicine analyses including the construction of AD-specific co-expression networks and genome-scale metabolic modelling of the brain in AD patients to identify key genes, metabolites and pathways involved in the progression of AD. We identified AMIGO1 and GRPRASP2 as examples of commonly altered marker genes in AD patients. Moreover, we found alterations in energy metabolism, represented by reduced oxidative phosphorylation and ATPase activity, as well as the depletion of hexanoyl-CoA, pentanoyl-CoA, (2E)-hexenoyl-CoA and numerous other unsaturated fatty acids in the brain. We also observed that neuroprotective metabolites (e.g., vitamins, retinoids and unsaturated fatty acids) tend to be depleted in the AD brain, while neurotoxic metabolites (e.g., β-alanine, bilirubin) were more abundant. In summary, we systematically revealed the key genes and pathways related to the progression of AD, gained insight into the crucial mechanisms of AD and identified some possible targets that could be used in the treatment of AD.
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spelling pubmed-85842432021-11-12 Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis Bayraktar, Abdulahad Lam, Simon Altay, Ozlem Li, Xiangyu Yuan, Meng Zhang, Cheng Arif, Muhammad Turkez, Hasan Uhlén, Mathias Shoaie, Saeed Mardinoglu, Adil Int J Mol Sci Article The complex pathology of Alzheimer’s disease (AD) emphasises the need for comprehensive modelling of the disease, which may lead to the development of efficient treatment strategies. To address this challenge, we analysed transcriptome data of post-mortem human brain samples of healthy elders and individuals with late-onset AD from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MayoRNAseq) studies in the AMP-AD consortium. In this context, we conducted several bioinformatics and systems medicine analyses including the construction of AD-specific co-expression networks and genome-scale metabolic modelling of the brain in AD patients to identify key genes, metabolites and pathways involved in the progression of AD. We identified AMIGO1 and GRPRASP2 as examples of commonly altered marker genes in AD patients. Moreover, we found alterations in energy metabolism, represented by reduced oxidative phosphorylation and ATPase activity, as well as the depletion of hexanoyl-CoA, pentanoyl-CoA, (2E)-hexenoyl-CoA and numerous other unsaturated fatty acids in the brain. We also observed that neuroprotective metabolites (e.g., vitamins, retinoids and unsaturated fatty acids) tend to be depleted in the AD brain, while neurotoxic metabolites (e.g., β-alanine, bilirubin) were more abundant. In summary, we systematically revealed the key genes and pathways related to the progression of AD, gained insight into the crucial mechanisms of AD and identified some possible targets that could be used in the treatment of AD. MDPI 2021-10-26 /pmc/articles/PMC8584243/ /pubmed/34768988 http://dx.doi.org/10.3390/ijms222111556 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bayraktar, Abdulahad
Lam, Simon
Altay, Ozlem
Li, Xiangyu
Yuan, Meng
Zhang, Cheng
Arif, Muhammad
Turkez, Hasan
Uhlén, Mathias
Shoaie, Saeed
Mardinoglu, Adil
Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_full Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_fullStr Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_full_unstemmed Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_short Revealing the Molecular Mechanisms of Alzheimer’s Disease Based on Network Analysis
title_sort revealing the molecular mechanisms of alzheimer’s disease based on network analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584243/
https://www.ncbi.nlm.nih.gov/pubmed/34768988
http://dx.doi.org/10.3390/ijms222111556
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