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Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) proteins in the form of plaques that cause a proteostasis imbalance in the brain. Several studies have identified autophagy deficits in both AD patients and AD animal models. H...

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Autores principales: Lin, Hongru, Gao, Yehui, Zhang, Chen, Ma, Botian, Wu, Mengchen, Cui, Xianghuan, Wang, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133694/
https://www.ncbi.nlm.nih.gov/pubmed/35645788
http://dx.doi.org/10.3389/fnagi.2022.885145
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author Lin, Hongru
Gao, Yehui
Zhang, Chen
Ma, Botian
Wu, Mengchen
Cui, Xianghuan
Wang, Hongbing
author_facet Lin, Hongru
Gao, Yehui
Zhang, Chen
Ma, Botian
Wu, Mengchen
Cui, Xianghuan
Wang, Hongbing
author_sort Lin, Hongru
collection PubMed
description Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) proteins in the form of plaques that cause a proteostasis imbalance in the brain. Several studies have identified autophagy deficits in both AD patients and AD animal models. Here, we used transgenic Caenorhabditis elegans to study the relationship between autophagy flux and Aβ. We labeled autophagosomes with an advanced fluorescence reporter system, and used this to observe that human Aβ expression caused autophagosome accumulation in C. elegans muscle. The autophagy-related drugs chloroquine and 3-MA were employed to investigate the relationship between changes in autophagic flux and the toxicity of Aβ expression. We found that reducing autophagosome accumulation delayed Aβ-induced paralysis in the CL4176 strain of C. elegans, and alleviated Aβ-induced toxicity, thus having a neuroprotective effect. Finally, we used RNA-sequencing and proteomics to identify genes whose expression was affected by Aβ aggregation in C. elegans. We identified a series of enriched autophagy-related signal pathways, suggesting that autophagosome accumulation impairs Aβ protein homeostasis in nematodes. Thus, maintaining normal autophagy levels appears to be important in repairing the protein homeostasis imbalance caused by Aβ expression.
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spelling pubmed-91336942022-05-27 Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans Lin, Hongru Gao, Yehui Zhang, Chen Ma, Botian Wu, Mengchen Cui, Xianghuan Wang, Hongbing Front Aging Neurosci Neuroscience Alzheimer’s disease (AD) is a progressive, neurodegenerative disease characterized by the accumulation of amyloid-beta (Aβ) proteins in the form of plaques that cause a proteostasis imbalance in the brain. Several studies have identified autophagy deficits in both AD patients and AD animal models. Here, we used transgenic Caenorhabditis elegans to study the relationship between autophagy flux and Aβ. We labeled autophagosomes with an advanced fluorescence reporter system, and used this to observe that human Aβ expression caused autophagosome accumulation in C. elegans muscle. The autophagy-related drugs chloroquine and 3-MA were employed to investigate the relationship between changes in autophagic flux and the toxicity of Aβ expression. We found that reducing autophagosome accumulation delayed Aβ-induced paralysis in the CL4176 strain of C. elegans, and alleviated Aβ-induced toxicity, thus having a neuroprotective effect. Finally, we used RNA-sequencing and proteomics to identify genes whose expression was affected by Aβ aggregation in C. elegans. We identified a series of enriched autophagy-related signal pathways, suggesting that autophagosome accumulation impairs Aβ protein homeostasis in nematodes. Thus, maintaining normal autophagy levels appears to be important in repairing the protein homeostasis imbalance caused by Aβ expression. Frontiers Media S.A. 2022-05-12 /pmc/articles/PMC9133694/ /pubmed/35645788 http://dx.doi.org/10.3389/fnagi.2022.885145 Text en Copyright © 2022 Lin, Gao, Zhang, Ma, Wu, Cui and Wang. 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
Lin, Hongru
Gao, Yehui
Zhang, Chen
Ma, Botian
Wu, Mengchen
Cui, Xianghuan
Wang, Hongbing
Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans
title Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans
title_full Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans
title_fullStr Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans
title_full_unstemmed Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans
title_short Autophagy Regulation Influences β-Amyloid Toxicity in Transgenic Caenorhabditis elegans
title_sort autophagy regulation influences β-amyloid toxicity in transgenic caenorhabditis elegans
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9133694/
https://www.ncbi.nlm.nih.gov/pubmed/35645788
http://dx.doi.org/10.3389/fnagi.2022.885145
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