Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification
BACKGROUND: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Abeta aggregation in vivo are poorly understood, as well as the cellular mean...
Published in: | Molecular Neurodegeneration |
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ftumelbourne:oai:jupiter.its.unimelb.edu.au:11343/51273 2023-05-15T15:09:58+02:00 Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification Minniti, AN Rebolledo, DL Grez, PM Fadic, R Aldunate, R Volitakis, I Cherny, RA Opazo, C Masters, C Bush, AI Inestrosa, NC 2009-01-06 http://hdl.handle.net/11343/51273 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000266063200002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c https://doi.org/10.1186/1750-1326-4-2 English eng BMC doi:10.1186/1750-1326-4-2 issn:1750-1326 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000266063200002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c ARTN 2 Minniti, AN; Rebolledo, DL; Grez, PM; Fadic, R; Aldunate, R; Volitakis, I; Cherny, RA; Opazo, C; Masters, C; Bush, AI; Inestrosa, NC, Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification, MOLECULAR NEURODEGENERATION, 2009, 4 1750-1326 http://hdl.handle.net/11343/51273 Journal Article 2009 ftumelbourne https://doi.org/10.1186/1750-1326-4-2 2019-10-15T12:11:52Z BACKGROUND: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Abeta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Abeta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Abeta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. RESULTS: In the present work, we found that intracellular Abeta aggregation in muscle cells of Caenorhabditis elegans overexpressing Abeta peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Abeta. We show that intracellular amyloid aggregation of wild type Abeta is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Abeta-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. CONCLUSION: Our data show that intracellular Abeta amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Abeta aggregation may be part of a cell protective mechanism. Article in Journal/Newspaper Arctic The University of Melbourne: Digital Repository Arctic Molecular Neurodegeneration 4 1 2 |
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Open Polar |
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The University of Melbourne: Digital Repository |
op_collection_id |
ftumelbourne |
language |
English |
description |
BACKGROUND: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Abeta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Abeta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Abeta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. RESULTS: In the present work, we found that intracellular Abeta aggregation in muscle cells of Caenorhabditis elegans overexpressing Abeta peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Abeta. We show that intracellular amyloid aggregation of wild type Abeta is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Abeta-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. CONCLUSION: Our data show that intracellular Abeta amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Abeta aggregation may be part of a cell protective mechanism. |
format |
Article in Journal/Newspaper |
author |
Minniti, AN Rebolledo, DL Grez, PM Fadic, R Aldunate, R Volitakis, I Cherny, RA Opazo, C Masters, C Bush, AI Inestrosa, NC |
spellingShingle |
Minniti, AN Rebolledo, DL Grez, PM Fadic, R Aldunate, R Volitakis, I Cherny, RA Opazo, C Masters, C Bush, AI Inestrosa, NC Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
author_facet |
Minniti, AN Rebolledo, DL Grez, PM Fadic, R Aldunate, R Volitakis, I Cherny, RA Opazo, C Masters, C Bush, AI Inestrosa, NC |
author_sort |
Minniti, AN |
title |
Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_short |
Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_full |
Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_fullStr |
Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_full_unstemmed |
Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_sort |
intracellular amyloid formation in muscle cells of a beta-transgenic caenorhabditis elegans: determinants and physiological role in copper detoxification |
publisher |
BMC |
publishDate |
2009 |
url |
http://hdl.handle.net/11343/51273 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000266063200002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c https://doi.org/10.1186/1750-1326-4-2 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_relation |
doi:10.1186/1750-1326-4-2 issn:1750-1326 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000266063200002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c ARTN 2 Minniti, AN; Rebolledo, DL; Grez, PM; Fadic, R; Aldunate, R; Volitakis, I; Cherny, RA; Opazo, C; Masters, C; Bush, AI; Inestrosa, NC, Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification, MOLECULAR NEURODEGENERATION, 2009, 4 1750-1326 http://hdl.handle.net/11343/51273 |
op_doi |
https://doi.org/10.1186/1750-1326-4-2 |
container_title |
Molecular Neurodegeneration |
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4 |
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1 |
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2 |
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1766341050012532736 |