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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8584243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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