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<sup...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/4/1835 |
| Summary: | 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<sup>3+</sup>) is the most ubiquitous neurotoxic metal on earth, extensively bioavailable to humans. Despite this, the link between Al<sup>3+</sup> and AD has been debated for decades and remains controversial. Using <i>Saccharomyces cerevisiae</i> as a model organism expressing Aβ42, this study aimed to examine the mechanisms of Al<sup>3+</sup> toxicity and its interactions with Aβ42. <i>S. cerevisiae</i> cells producing Aβ42 treated with varying concentrations of Al<sup>3+</sup> were examined for cell viability, growth inhibition, and production of reactive oxygen species (ROS). Al<sup>3+</sup> 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<sup>3+</sup> greatly inhibited the fermentative growth of yeast producing GFP–Aβ42, which was enhanced by ferric iron (Fe<sup>3+</sup>), while there was negligible growth inhibition of GFP cells. Al<sup>3+</sup>- induced ROS levels in yeast expressing native Aβ42 were significantly higher than in empty vector controls. These findings demonstrate Al<sup>3+</sup> has a direct, detrimental toxic synergy with Aβ42 that can be influenced by Fe<sup>3+</sup>, causing increased oxidative stress. Thus, Al<sup>3+</sup> should be considered as an important factor, alongside the known characteristic hallmarks of AD, in the development and aetiology of the disease. |
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| ISSN: | 1661-6596 1422-0067 |