Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification
Abstract Background The amyloid β-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 Aβ aggregation in vivo are poorly understood, as well as the cellular me...
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ftbiomed:oai:biomedcentral.com:1750-1326-4-2 2023-05-15T15:10:03+02:00 Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification Minniti, Alicia N Rebolledo, Daniela L Grez, Paula M Fadic, Ricardo Aldunate, Rebeca Volitakis, Irene Cherny, Robert A Opazo, Carlos Masters, Colin Bush, Ashley I Inestrosa, Nibaldo C 2009-01-06 http://www.molecularneurodegeneration.com/content/4/1/2 en eng BioMed Central Ltd. http://www.molecularneurodegeneration.com/content/4/1/2 Copyright 2009 Minniti et al; licensee BioMed Central Ltd. Research article 2009 ftbiomed 2009-04-03T00:31:27Z Abstract Background The amyloid β-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 Aβ 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 Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ 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 Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu 2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu 2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu 2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism. Article in Journal/Newspaper Arctic BioMed Central Arctic |
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description |
Abstract Background The amyloid β-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 Aβ 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 Aβ is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Aβ 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 Aβ aggregation in muscle cells of Caenorhabditis elegans overexpressing Aβ peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Aβ. We show that intracellular amyloid aggregation of wild type Aβ is accelerated by Cu 2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Aβ-transgenic worms display a higher tolerance to Cu 2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion Our data show that intracellular Aβ amyloid aggregates may trap excess of free Cu 2+ buffering its cytotoxic effects and that accelerated intracellular Aβ aggregation may be part of a cell protective mechanism. |
format |
Article in Journal/Newspaper |
author |
Minniti, Alicia N Rebolledo, Daniela L Grez, Paula M Fadic, Ricardo Aldunate, Rebeca Volitakis, Irene Cherny, Robert A Opazo, Carlos Masters, Colin Bush, Ashley I Inestrosa, Nibaldo C |
spellingShingle |
Minniti, Alicia N Rebolledo, Daniela L Grez, Paula M Fadic, Ricardo Aldunate, Rebeca Volitakis, Irene Cherny, Robert A Opazo, Carlos Masters, Colin Bush, Ashley I Inestrosa, Nibaldo C Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
author_facet |
Minniti, Alicia N Rebolledo, Daniela L Grez, Paula M Fadic, Ricardo Aldunate, Rebeca Volitakis, Irene Cherny, Robert A Opazo, Carlos Masters, Colin Bush, Ashley I Inestrosa, Nibaldo C |
author_sort |
Minniti, Alicia N |
title |
Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_short |
Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_full |
Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_fullStr |
Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_full_unstemmed |
Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification |
title_sort |
intracellular amyloid formation in muscle cells of aβ-transgenic caenorhabditis elegans: determinants and physiological role in copper detoxification |
publisher |
BioMed Central Ltd. |
publishDate |
2009 |
url |
http://www.molecularneurodegeneration.com/content/4/1/2 |
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Arctic |
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Arctic |
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Arctic |
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Arctic |
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http://www.molecularneurodegeneration.com/content/4/1/2 |
op_rights |
Copyright 2009 Minniti et al; licensee BioMed Central Ltd. |
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1766341122670460928 |