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Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models
The most accepted hypothesis in Alzheimer’s disease (AD) is the amyloid cascade which establishes that Aβ accumulation may induce the disease development. This accumulation may occur years before the clinical symptoms but it has not been elucidated if this accumulation is the cause or the consequenc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203760/ https://www.ncbi.nlm.nih.gov/pubmed/35710783 http://dx.doi.org/10.1038/s41598-022-13683-3 |
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author | de la Cueva, Macarena Antequera, Desiree Ordoñez-Gutierrez, Lara Wandosell, Francisco Camins, Antonio Carro, Eva Bartolome, Fernando |
author_facet | de la Cueva, Macarena Antequera, Desiree Ordoñez-Gutierrez, Lara Wandosell, Francisco Camins, Antonio Carro, Eva Bartolome, Fernando |
author_sort | de la Cueva, Macarena |
collection | PubMed |
description | The most accepted hypothesis in Alzheimer’s disease (AD) is the amyloid cascade which establishes that Aβ accumulation may induce the disease development. This accumulation may occur years before the clinical symptoms but it has not been elucidated if this accumulation is the cause or the consequence of AD. It is however, clear that Aβ accumulation exerts toxic effects in the cerebral cells. It is important then to investigate all possible associated events that may help to design new therapeutic strategies to defeat or ameliorate the symptoms in AD. Alterations in the mitochondrial physiology have been found in AD but it is not still clear if they could be an early event in the disease progression associated to amyloidosis or other conditions. Using APP/PS1 mice, our results support published evidence and show imbalances in the mitochondrial dynamics in the cerebral cortex and hippocampus of these mice representing very early events in the disease progression. We demonstrate in cellular models that these imbalances are consequence of Aβ accumulation that ultimately induce increased mitophagy, a mechanism which selectively removes damaged mitochondria by autophagy. Along with increased mitophagy, we also found that Aβ independently increases autophagy in APP/PS1 mice. Therefore, mitochondrial dysfunction could be an early feature in AD, associated with amyloid overload. |
format | Online Article Text |
id | pubmed-9203760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-92037602022-06-18 Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models de la Cueva, Macarena Antequera, Desiree Ordoñez-Gutierrez, Lara Wandosell, Francisco Camins, Antonio Carro, Eva Bartolome, Fernando Sci Rep Article The most accepted hypothesis in Alzheimer’s disease (AD) is the amyloid cascade which establishes that Aβ accumulation may induce the disease development. This accumulation may occur years before the clinical symptoms but it has not been elucidated if this accumulation is the cause or the consequence of AD. It is however, clear that Aβ accumulation exerts toxic effects in the cerebral cells. It is important then to investigate all possible associated events that may help to design new therapeutic strategies to defeat or ameliorate the symptoms in AD. Alterations in the mitochondrial physiology have been found in AD but it is not still clear if they could be an early event in the disease progression associated to amyloidosis or other conditions. Using APP/PS1 mice, our results support published evidence and show imbalances in the mitochondrial dynamics in the cerebral cortex and hippocampus of these mice representing very early events in the disease progression. We demonstrate in cellular models that these imbalances are consequence of Aβ accumulation that ultimately induce increased mitophagy, a mechanism which selectively removes damaged mitochondria by autophagy. Along with increased mitophagy, we also found that Aβ independently increases autophagy in APP/PS1 mice. Therefore, mitochondrial dysfunction could be an early feature in AD, associated with amyloid overload. Nature Publishing Group UK 2022-06-16 /pmc/articles/PMC9203760/ /pubmed/35710783 http://dx.doi.org/10.1038/s41598-022-13683-3 Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article de la Cueva, Macarena Antequera, Desiree Ordoñez-Gutierrez, Lara Wandosell, Francisco Camins, Antonio Carro, Eva Bartolome, Fernando Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models |
title | Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models |
title_full | Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models |
title_fullStr | Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models |
title_full_unstemmed | Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models |
title_short | Amyloid-β impairs mitochondrial dynamics and autophagy in Alzheimer’s disease experimental models |
title_sort | amyloid-β impairs mitochondrial dynamics and autophagy in alzheimer’s disease experimental models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203760/ https://www.ncbi.nlm.nih.gov/pubmed/35710783 http://dx.doi.org/10.1038/s41598-022-13683-3 |
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