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Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43

BACKGROUND: Cerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia. PURPOSE: This study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their...

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Autores principales: Wang, Xingqiao, Kong, Fanqiang, Lin, Zengbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10133528/
https://www.ncbi.nlm.nih.gov/pubmed/37122373
http://dx.doi.org/10.3389/fnagi.2023.1132733
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author Wang, Xingqiao
Kong, Fanqiang
Lin, Zengbin
author_facet Wang, Xingqiao
Kong, Fanqiang
Lin, Zengbin
author_sort Wang, Xingqiao
collection PubMed
description BACKGROUND: Cerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia. PURPOSE: This study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases. METHODS: Genes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments. RESULTS: The study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders. CONCLUSION: The findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.
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spelling pubmed-101335282023-04-28 Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43 Wang, Xingqiao Kong, Fanqiang Lin, Zengbin Front Aging Neurosci Neuroscience BACKGROUND: Cerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia. PURPOSE: This study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases. METHODS: Genes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments. RESULTS: The study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders. CONCLUSION: The findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia. Frontiers Media S.A. 2023-04-13 /pmc/articles/PMC10133528/ /pubmed/37122373 http://dx.doi.org/10.3389/fnagi.2023.1132733 Text en Copyright © 2023 Wang, Kong and Lin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Wang, Xingqiao
Kong, Fanqiang
Lin, Zengbin
Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43
title Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43
title_full Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43
title_fullStr Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43
title_full_unstemmed Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43
title_short Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43
title_sort cromolyn prevents cerebral vasospasm and dementia by targeting wdr43
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10133528/
https://www.ncbi.nlm.nih.gov/pubmed/37122373
http://dx.doi.org/10.3389/fnagi.2023.1132733
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