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Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex
Alzheimer’s disease (AD) is a chronic, neurodegenerative brain disorder affecting millions of Americans that is expected to increase in incidence with the expanding aging population. Symptomatic AD patients show cognitive decline and often develop neuropsychiatric symptoms due to the accumulation of...
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/PMC8069371/ https://www.ncbi.nlm.nih.gov/pubmed/33920138 http://dx.doi.org/10.3390/ijms22083915 |
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author | Bottero, Virginie Powers, Dallen Yalamanchi, Ashna Quinn, James P. Potashkin, Judith A. |
author_facet | Bottero, Virginie Powers, Dallen Yalamanchi, Ashna Quinn, James P. Potashkin, Judith A. |
author_sort | Bottero, Virginie |
collection | PubMed |
description | Alzheimer’s disease (AD) is a chronic, neurodegenerative brain disorder affecting millions of Americans that is expected to increase in incidence with the expanding aging population. Symptomatic AD patients show cognitive decline and often develop neuropsychiatric symptoms due to the accumulation of insoluble proteins that produce plaques and tangles seen in the brain at autopsy. Unexpectedly, some clinically normal individuals also show AD pathology in the brain at autopsy (asymptomatic AD, AsymAD). In this study, SWItchMiner software was used to identify key switch genes in the brain’s entorhinal cortex that lead to the development of AD or disease resilience. Seventy-two switch genes were identified that are differentially expressed in AD patients compared to healthy controls. These genes are involved in inflammation, platelet activation, and phospholipase D and estrogen signaling. Peroxisome proliferator-activated receptor γ (PPARG), zinc-finger transcription factor (YY1), sterol regulatory element-binding transcription factor 2 (SREBF2), and early growth response 1 (EGR1) were identified as transcription factors that potentially regulate switch genes in AD. Comparing AD patients to AsymAD individuals revealed 51 switch genes; PPARG as a potential regulator of these genes, and platelet activation and phospholipase D as critical signaling pathways. Chemical–protein interaction analysis revealed that valproic acid is a therapeutic agent that could prevent AD from progressing. |
format | Online Article Text |
id | pubmed-8069371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80693712021-04-26 Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex Bottero, Virginie Powers, Dallen Yalamanchi, Ashna Quinn, James P. Potashkin, Judith A. Int J Mol Sci Article Alzheimer’s disease (AD) is a chronic, neurodegenerative brain disorder affecting millions of Americans that is expected to increase in incidence with the expanding aging population. Symptomatic AD patients show cognitive decline and often develop neuropsychiatric symptoms due to the accumulation of insoluble proteins that produce plaques and tangles seen in the brain at autopsy. Unexpectedly, some clinically normal individuals also show AD pathology in the brain at autopsy (asymptomatic AD, AsymAD). In this study, SWItchMiner software was used to identify key switch genes in the brain’s entorhinal cortex that lead to the development of AD or disease resilience. Seventy-two switch genes were identified that are differentially expressed in AD patients compared to healthy controls. These genes are involved in inflammation, platelet activation, and phospholipase D and estrogen signaling. Peroxisome proliferator-activated receptor γ (PPARG), zinc-finger transcription factor (YY1), sterol regulatory element-binding transcription factor 2 (SREBF2), and early growth response 1 (EGR1) were identified as transcription factors that potentially regulate switch genes in AD. Comparing AD patients to AsymAD individuals revealed 51 switch genes; PPARG as a potential regulator of these genes, and platelet activation and phospholipase D as critical signaling pathways. Chemical–protein interaction analysis revealed that valproic acid is a therapeutic agent that could prevent AD from progressing. MDPI 2021-04-10 /pmc/articles/PMC8069371/ /pubmed/33920138 http://dx.doi.org/10.3390/ijms22083915 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 Bottero, Virginie Powers, Dallen Yalamanchi, Ashna Quinn, James P. Potashkin, Judith A. Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex |
title | Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex |
title_full | Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex |
title_fullStr | Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex |
title_full_unstemmed | Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex |
title_short | Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex |
title_sort | key disease mechanisms linked to alzheimer’s disease in the entorhinal cortex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069371/ https://www.ncbi.nlm.nih.gov/pubmed/33920138 http://dx.doi.org/10.3390/ijms22083915 |
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