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A Toxic Synergy between Aluminium and Amyloid Beta in Yeast
Alzheimer’s disease (AD), the most prevalent, age-related, neurodegenerative disease, is associated with the accumulation of amyloid beta (Aβ) and oxidative stress. However, the sporadic nature of late-onset AD has suggested that other factors, such as aluminium may be involved. Aluminium (Al(3+)) i...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918211/ https://www.ncbi.nlm.nih.gov/pubmed/33673244 http://dx.doi.org/10.3390/ijms22041835 |
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author | Mcdonald, Jamieson B. Dhakal, Sudip Macreadie, Ian |
author_facet | Mcdonald, Jamieson B. Dhakal, Sudip Macreadie, Ian |
author_sort | Mcdonald, Jamieson B. |
collection | PubMed |
description | Alzheimer’s disease (AD), the most prevalent, age-related, neurodegenerative disease, is associated with the accumulation of amyloid beta (Aβ) and oxidative stress. However, the sporadic nature of late-onset AD has suggested that other factors, such as aluminium may be involved. Aluminium (Al(3+)) is the most ubiquitous neurotoxic metal on earth, extensively bioavailable to humans. Despite this, the link between Al(3+) and AD has been debated for decades and remains controversial. Using Saccharomyces cerevisiae as a model organism expressing Aβ42, this study aimed to examine the mechanisms of Al(3+) toxicity and its interactions with Aβ42. S. cerevisiae cells producing Aβ42 treated with varying concentrations of Al(3+) were examined for cell viability, growth inhibition, and production of reactive oxygen species (ROS). Al(3+) caused a significant reduction in cell viability: cell death in yeast producing green fluorescent protein tagged with Aβ42 (GFP–Aβ42) was significantly higher than in cells producing green fluorescent protein (GFP) alone. Additionally, Al(3+) greatly inhibited the fermentative growth of yeast producing GFP–Aβ42, which was enhanced by ferric iron (Fe(3+)), while there was negligible growth inhibition of GFP cells. Al(3+)- induced ROS levels in yeast expressing native Aβ42 were significantly higher than in empty vector controls. These findings demonstrate Al(3+) has a direct, detrimental toxic synergy with Aβ42 that can be influenced by Fe(3+), causing increased oxidative stress. Thus, Al(3+) should be considered as an important factor, alongside the known characteristic hallmarks of AD, in the development and aetiology of the disease. |
format | Online Article Text |
id | pubmed-7918211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79182112021-03-02 A Toxic Synergy between Aluminium and Amyloid Beta in Yeast Mcdonald, Jamieson B. Dhakal, Sudip Macreadie, Ian Int J Mol Sci Article Alzheimer’s disease (AD), the most prevalent, age-related, neurodegenerative disease, is associated with the accumulation of amyloid beta (Aβ) and oxidative stress. However, the sporadic nature of late-onset AD has suggested that other factors, such as aluminium may be involved. Aluminium (Al(3+)) is the most ubiquitous neurotoxic metal on earth, extensively bioavailable to humans. Despite this, the link between Al(3+) and AD has been debated for decades and remains controversial. Using Saccharomyces cerevisiae as a model organism expressing Aβ42, this study aimed to examine the mechanisms of Al(3+) toxicity and its interactions with Aβ42. S. cerevisiae cells producing Aβ42 treated with varying concentrations of Al(3+) were examined for cell viability, growth inhibition, and production of reactive oxygen species (ROS). Al(3+) caused a significant reduction in cell viability: cell death in yeast producing green fluorescent protein tagged with Aβ42 (GFP–Aβ42) was significantly higher than in cells producing green fluorescent protein (GFP) alone. Additionally, Al(3+) greatly inhibited the fermentative growth of yeast producing GFP–Aβ42, which was enhanced by ferric iron (Fe(3+)), while there was negligible growth inhibition of GFP cells. Al(3+)- induced ROS levels in yeast expressing native Aβ42 were significantly higher than in empty vector controls. These findings demonstrate Al(3+) has a direct, detrimental toxic synergy with Aβ42 that can be influenced by Fe(3+), causing increased oxidative stress. Thus, Al(3+) should be considered as an important factor, alongside the known characteristic hallmarks of AD, in the development and aetiology of the disease. MDPI 2021-02-12 /pmc/articles/PMC7918211/ /pubmed/33673244 http://dx.doi.org/10.3390/ijms22041835 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mcdonald, Jamieson B. Dhakal, Sudip Macreadie, Ian A Toxic Synergy between Aluminium and Amyloid Beta in Yeast |
title | A Toxic Synergy between Aluminium and Amyloid Beta in Yeast |
title_full | A Toxic Synergy between Aluminium and Amyloid Beta in Yeast |
title_fullStr | A Toxic Synergy between Aluminium and Amyloid Beta in Yeast |
title_full_unstemmed | A Toxic Synergy between Aluminium and Amyloid Beta in Yeast |
title_short | A Toxic Synergy between Aluminium and Amyloid Beta in Yeast |
title_sort | toxic synergy between aluminium and amyloid beta in yeast |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918211/ https://www.ncbi.nlm.nih.gov/pubmed/33673244 http://dx.doi.org/10.3390/ijms22041835 |
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