Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease
The mechanism by which aggregates of the β-amyloid peptide (Aβ) mediate their toxicity is uncertain. We show here that the expression of the 42-amino-acid isoform of Aβ (Aβ1–42) changes the expression of genes involved in oxidative stress in a Drosophila model of Alzheimer’s disease. A subsequent ge...
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ftpubmed:oai:pubmedcentral.nih.gov:2777252 2023-05-15T14:57:58+02:00 Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease Rival, Thomas Page, Richard M Chandraratna, Dhianjali S Sendall, Timothy J Ryder, Edward Liu, Beinan Lewis, Huw Rosahl, Thomas Hider, Robert Camargo, L M Shearman, Mark S Crowther, Damian C Lomas, David A 2009-04 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777252 http://www.ncbi.nlm.nih.gov/pubmed/19519625 https://doi.org/10.1111/j.1460-9568.2009.06701.x en eng Blackwell Publishing Ltd http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777252 http://www.ncbi.nlm.nih.gov/pubmed/19519625 http://dx.doi.org/10.1111/j.1460-9568.2009.06701.x Journal compilation © 2009 Federation of European Neuroscience Societies and Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. CC-BY Molecular and Developmental Neuroscience Text 2009 ftpubmed https://doi.org/10.1111/j.1460-9568.2009.06701.x 2013-09-02T18:49:02Z The mechanism by which aggregates of the β-amyloid peptide (Aβ) mediate their toxicity is uncertain. We show here that the expression of the 42-amino-acid isoform of Aβ (Aβ1–42) changes the expression of genes involved in oxidative stress in a Drosophila model of Alzheimer’s disease. A subsequent genetic screen confirmed the importance of oxidative stress and a molecular dissection of the steps in the cellular metabolism of reactive oxygen species revealed that the iron-binding protein ferritin and the H2O2 scavenger catalase are the most potent suppressors of the toxicity of wild-type and Arctic (E22G) Aβ1–42. Likewise, treatment with the iron-binding compound clioquinol increased the lifespan of flies expressing Arctic Aβ1–42. The effect of iron appears to be mediated by oxidative stress as ferritin heavy chain co-expression reduced carbonyl levels in Aβ1–42 flies by 65% and restored the survival and locomotion function to normal. This was achieved despite the presence of elevated levels of the Aβ1–42. Taken together, our data show that oxidative stress, probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential for Aβ1–42 toxicity in vivo and provide strong support for Alzheimer’s disease therapies based on metal chelation. Text Arctic PubMed Central (PMC) Arctic Fenton ENVELOPE(161.917,161.917,-74.333,-74.333) European Journal of Neuroscience 29 7 1335 1347 |
institution |
Open Polar |
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PubMed Central (PMC) |
op_collection_id |
ftpubmed |
language |
English |
topic |
Molecular and Developmental Neuroscience |
spellingShingle |
Molecular and Developmental Neuroscience Rival, Thomas Page, Richard M Chandraratna, Dhianjali S Sendall, Timothy J Ryder, Edward Liu, Beinan Lewis, Huw Rosahl, Thomas Hider, Robert Camargo, L M Shearman, Mark S Crowther, Damian C Lomas, David A Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease |
topic_facet |
Molecular and Developmental Neuroscience |
description |
The mechanism by which aggregates of the β-amyloid peptide (Aβ) mediate their toxicity is uncertain. We show here that the expression of the 42-amino-acid isoform of Aβ (Aβ1–42) changes the expression of genes involved in oxidative stress in a Drosophila model of Alzheimer’s disease. A subsequent genetic screen confirmed the importance of oxidative stress and a molecular dissection of the steps in the cellular metabolism of reactive oxygen species revealed that the iron-binding protein ferritin and the H2O2 scavenger catalase are the most potent suppressors of the toxicity of wild-type and Arctic (E22G) Aβ1–42. Likewise, treatment with the iron-binding compound clioquinol increased the lifespan of flies expressing Arctic Aβ1–42. The effect of iron appears to be mediated by oxidative stress as ferritin heavy chain co-expression reduced carbonyl levels in Aβ1–42 flies by 65% and restored the survival and locomotion function to normal. This was achieved despite the presence of elevated levels of the Aβ1–42. Taken together, our data show that oxidative stress, probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential for Aβ1–42 toxicity in vivo and provide strong support for Alzheimer’s disease therapies based on metal chelation. |
format |
Text |
author |
Rival, Thomas Page, Richard M Chandraratna, Dhianjali S Sendall, Timothy J Ryder, Edward Liu, Beinan Lewis, Huw Rosahl, Thomas Hider, Robert Camargo, L M Shearman, Mark S Crowther, Damian C Lomas, David A |
author_facet |
Rival, Thomas Page, Richard M Chandraratna, Dhianjali S Sendall, Timothy J Ryder, Edward Liu, Beinan Lewis, Huw Rosahl, Thomas Hider, Robert Camargo, L M Shearman, Mark S Crowther, Damian C Lomas, David A |
author_sort |
Rival, Thomas |
title |
Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease |
title_short |
Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease |
title_full |
Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease |
title_fullStr |
Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease |
title_full_unstemmed |
Fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a Drosophila model of Alzheimer’s disease |
title_sort |
fenton chemistry and oxidative stress mediate the toxicity of the β-amyloid peptide in a drosophila model of alzheimer’s disease |
publisher |
Blackwell Publishing Ltd |
publishDate |
2009 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777252 http://www.ncbi.nlm.nih.gov/pubmed/19519625 https://doi.org/10.1111/j.1460-9568.2009.06701.x |
long_lat |
ENVELOPE(161.917,161.917,-74.333,-74.333) |
geographic |
Arctic Fenton |
geographic_facet |
Arctic Fenton |
genre |
Arctic |
genre_facet |
Arctic |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777252 http://www.ncbi.nlm.nih.gov/pubmed/19519625 http://dx.doi.org/10.1111/j.1460-9568.2009.06701.x |
op_rights |
Journal compilation © 2009 Federation of European Neuroscience Societies and Blackwell Publishing Ltd http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1111/j.1460-9568.2009.06701.x |
container_title |
European Journal of Neuroscience |
container_volume |
29 |
container_issue |
7 |
container_start_page |
1335 |
op_container_end_page |
1347 |
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1766330052113334272 |