Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1784713625698566144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9133694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT linhongru autophagyregulationinfluencesbamyloidtoxicityintransgeniccaenorhabditiselegans AT gaoyehui autophagyregulationinfluencesbamyloidtoxicityintransgeniccaenorhabditiselegans AT zhangchen autophagyregulationinfluencesbamyloidtoxicityintransgeniccaenorhabditiselegans AT mabotian autophagyregulationinfluencesbamyloidtoxicityintransgeniccaenorhabditiselegans AT wumengchen autophagyregulationinfluencesbamyloidtoxicityintransgeniccaenorhabditiselegans AT cuixianghuan autophagyregulationinfluencesbamyloidtoxicityintransgeniccaenorhabditiselegans AT wanghongbing autophagyregulationinfluencesbamyloidtoxicityintransgeniccaenorhabditiselegans |