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A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells

Amyotrophic lateral sclerosis (ALS) is caused by selective the loss of spinal motor neurons by multifactorial pathological mechanisms and results in muscle atrophy. Incidence rates of ALS are increasing over time, but there are no effective treatments at present due to limitations on approved therap...

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Autor principal: Yang, Eun Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490039/
https://www.ncbi.nlm.nih.gov/pubmed/34616479
http://dx.doi.org/10.1155/2021/6773260
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author Yang, Eun Jin
author_facet Yang, Eun Jin
author_sort Yang, Eun Jin
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is caused by selective the loss of spinal motor neurons by multifactorial pathological mechanisms and results in muscle atrophy. Incidence rates of ALS are increasing over time, but there are no effective treatments at present due to limitations on approved therapies (riluzole and edaravone). Therefore, this study investigated whether combined treatment with Bojungikgi-tang and riluzole could act synergistically in transactive response DNA-binding protein 43 (TDP-43) stress granule cells. To examine the effect of combined treatment on oxidative stress-induced cell death, the CCK8 assay was performed for the detection of cell viability. The expression of oxidative stress-induced proteins was determined by Western blot. Quantification of sodium arsenite-induced reactive oxygen species (ROS) was measured in TDP-43 stress granular cells using 2,7-diacetyl dichlorofluorescein diacetate. To investigate the effect of combined treatment on TDP-43 aggregation, immunofluorescence and immunoblotting were performed in TDP-43 stress granular cells. This combined treatment alleviated oxidative stress-induced cell death by increasing the expression levels of antioxidation proteins, such as heme oxygenase-1 and B cell lymphoma-2-associated X protein. Furthermore, it reduced oxidative stress-induced TDP-43 aggregates and lowered the levels of autophagy-related proteins, including p62, light chain 3b, and ATG8, in TDP-43-expressing cells. Our results suggest that this combined treatment could be helpful for autophagy regulation in other neurodegenerative diseases.
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spelling pubmed-84900392021-10-05 A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells Yang, Eun Jin Evid Based Complement Alternat Med Research Article Amyotrophic lateral sclerosis (ALS) is caused by selective the loss of spinal motor neurons by multifactorial pathological mechanisms and results in muscle atrophy. Incidence rates of ALS are increasing over time, but there are no effective treatments at present due to limitations on approved therapies (riluzole and edaravone). Therefore, this study investigated whether combined treatment with Bojungikgi-tang and riluzole could act synergistically in transactive response DNA-binding protein 43 (TDP-43) stress granule cells. To examine the effect of combined treatment on oxidative stress-induced cell death, the CCK8 assay was performed for the detection of cell viability. The expression of oxidative stress-induced proteins was determined by Western blot. Quantification of sodium arsenite-induced reactive oxygen species (ROS) was measured in TDP-43 stress granular cells using 2,7-diacetyl dichlorofluorescein diacetate. To investigate the effect of combined treatment on TDP-43 aggregation, immunofluorescence and immunoblotting were performed in TDP-43 stress granular cells. This combined treatment alleviated oxidative stress-induced cell death by increasing the expression levels of antioxidation proteins, such as heme oxygenase-1 and B cell lymphoma-2-associated X protein. Furthermore, it reduced oxidative stress-induced TDP-43 aggregates and lowered the levels of autophagy-related proteins, including p62, light chain 3b, and ATG8, in TDP-43-expressing cells. Our results suggest that this combined treatment could be helpful for autophagy regulation in other neurodegenerative diseases. Hindawi 2021-09-27 /pmc/articles/PMC8490039/ /pubmed/34616479 http://dx.doi.org/10.1155/2021/6773260 Text en Copyright © 2021 Eun Jin Yang. 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
Yang, Eun Jin
A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells
title A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells
title_full A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells
title_fullStr A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells
title_full_unstemmed A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells
title_short A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells
title_sort novel supplement attenuates oxidative stress-induced tdp-43-related pathogenesis in tdp-43-expressed cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490039/
https://www.ncbi.nlm.nih.gov/pubmed/34616479
http://dx.doi.org/10.1155/2021/6773260
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