Fenton chemistry and oxidative stress mediate the toxicity of the β‐amyloid peptide in a Drosophila model of Alzheimer’s disease
Abstract 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 (Aβ 1–42 ) changes the expression of genes involved in oxidative stress in a Drosophila model of Alzheimer’s disease. A su...
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crwiley:10.1111/j.1460-9568.2009.06701.x 2024-09-09T19:23:34+00:00 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 http://dx.doi.org/10.1111/j.1460-9568.2009.06701.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1460-9568.2009.06701.x https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1460-9568.2009.06701.x en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor European Journal of Neuroscience volume 29, issue 7, page 1335-1347 ISSN 0953-816X 1460-9568 journal-article 2009 crwiley https://doi.org/10.1111/j.1460-9568.2009.06701.x 2024-08-27T04:26:20Z Abstract 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 (Aβ 1–42 ) 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 H 2 O 2 scavenger catalase are the most potent suppressors of the toxicity of wild‐type and Arctic (E22G) Aβ 1–42 . Likewise, treatment with the iron‐binding compound clioquinol increased the lifespan of flies expressing Arctic Aβ 1–42 . The effect of iron appears to be mediated by oxidative stress as ferritin heavy chain co‐expression reduced carbonyl levels in Aβ 1–42 flies by 65% and restored the survival and locomotion function to normal. This was achieved despite the presence of elevated levels of the Aβ 1–42 . Taken together, our data show that oxidative stress, probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential for Aβ 1–42 toxicity in vivo and provide strong support for Alzheimer’s disease therapies based on metal chelation. Article in Journal/Newspaper Arctic Wiley Online Library Arctic Fenton ENVELOPE(161.917,161.917,-74.333,-74.333) European Journal of Neuroscience 29 7 1335 1347 |
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Wiley Online Library |
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crwiley |
language |
English |
description |
Abstract 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 (Aβ 1–42 ) 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 H 2 O 2 scavenger catalase are the most potent suppressors of the toxicity of wild‐type and Arctic (E22G) Aβ 1–42 . Likewise, treatment with the iron‐binding compound clioquinol increased the lifespan of flies expressing Arctic Aβ 1–42 . The effect of iron appears to be mediated by oxidative stress as ferritin heavy chain co‐expression reduced carbonyl levels in Aβ 1–42 flies by 65% and restored the survival and locomotion function to normal. This was achieved despite the presence of elevated levels of the Aβ 1–42 . Taken together, our data show that oxidative stress, probably mediated by the hydroxyl radical and generated by the Fenton reaction, is essential for Aβ 1–42 toxicity in vivo and provide strong support for Alzheimer’s disease therapies based on metal chelation. |
format |
Article in Journal/Newspaper |
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. |
spellingShingle |
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 |
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 |
Wiley |
publishDate |
2009 |
url |
http://dx.doi.org/10.1111/j.1460-9568.2009.06701.x https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1460-9568.2009.06701.x https://onlinelibrary.wiley.com/doi/pdf/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_source |
European Journal of Neuroscience volume 29, issue 7, page 1335-1347 ISSN 0953-816X 1460-9568 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
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 |
_version_ |
1809893576667037696 |