Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease
Amyloid β-peptide (Aβ) is directly linked to Alzheimer's disease (AD). In its monomeric form, Aβ aggregates to produce fibrils and a range of oligomers, the latter being the most neurotoxic. Dysregulation of Ca2+ homeostasis in aging brains and in neurodegenerative disorders plays a crucial rol...
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ftpubmed:oai:pubmedcentral.nih.gov:3065491 2023-05-15T15:10:57+02:00 Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease Itkin, Anna Dupres, Vincent Dufrêne, Yves F. Bechinger, Burkhard Ruysschaert, Jean-Marie Raussens, Vincent 2011-03-28 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065491 http://www.ncbi.nlm.nih.gov/pubmed/21464905 https://doi.org/10.1371/journal.pone.0018250 en eng Public Library of Science http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065491 http://www.ncbi.nlm.nih.gov/pubmed/21464905 http://dx.doi.org/10.1371/journal.pone.0018250 Itkin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. CC-BY Research Article Text 2011 ftpubmed https://doi.org/10.1371/journal.pone.0018250 2013-09-03T12:44:11Z Amyloid β-peptide (Aβ) is directly linked to Alzheimer's disease (AD). In its monomeric form, Aβ aggregates to produce fibrils and a range of oligomers, the latter being the most neurotoxic. Dysregulation of Ca2+ homeostasis in aging brains and in neurodegenerative disorders plays a crucial role in numerous processes and contributes to cell dysfunction and death. Here we postulated that calcium may enable or accelerate the aggregation of Aβ. We compared the aggregation pattern of Aβ(1–40) and that of Aβ(1–40)E22G, an amyloid peptide carrying the Arctic mutation that causes early onset of the disease. We found that in the presence of Ca2+, Aβ(1–40) preferentially formed oligomers similar to those formed by Aβ(1–40)E22G with or without added Ca2+, whereas in the absence of added Ca2+ the Aβ(1–40) aggregated to form fibrils. Morphological similarities of the oligomers were confirmed by contact mode atomic force microscopy imaging. The distribution of oligomeric and fibrillar species in different samples was detected by gel electrophoresis and Western blot analysis, the results of which were further supported by thioflavin T fluorescence experiments. In the samples without Ca2+, Fourier transform infrared spectroscopy revealed conversion of oligomers from an anti-parallel β-sheet to the parallel β-sheet conformation characteristic of fibrils. Overall, these results led us to conclude that calcium ions stimulate the formation of oligomers of Aβ(1–40), that have been implicated in the pathogenesis of AD. Text Arctic PubMed Central (PMC) Arctic PLoS ONE 6 3 e18250 |
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Research Article Itkin, Anna Dupres, Vincent Dufrêne, Yves F. Bechinger, Burkhard Ruysschaert, Jean-Marie Raussens, Vincent Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease |
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Research Article |
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Amyloid β-peptide (Aβ) is directly linked to Alzheimer's disease (AD). In its monomeric form, Aβ aggregates to produce fibrils and a range of oligomers, the latter being the most neurotoxic. Dysregulation of Ca2+ homeostasis in aging brains and in neurodegenerative disorders plays a crucial role in numerous processes and contributes to cell dysfunction and death. Here we postulated that calcium may enable or accelerate the aggregation of Aβ. We compared the aggregation pattern of Aβ(1–40) and that of Aβ(1–40)E22G, an amyloid peptide carrying the Arctic mutation that causes early onset of the disease. We found that in the presence of Ca2+, Aβ(1–40) preferentially formed oligomers similar to those formed by Aβ(1–40)E22G with or without added Ca2+, whereas in the absence of added Ca2+ the Aβ(1–40) aggregated to form fibrils. Morphological similarities of the oligomers were confirmed by contact mode atomic force microscopy imaging. The distribution of oligomeric and fibrillar species in different samples was detected by gel electrophoresis and Western blot analysis, the results of which were further supported by thioflavin T fluorescence experiments. In the samples without Ca2+, Fourier transform infrared spectroscopy revealed conversion of oligomers from an anti-parallel β-sheet to the parallel β-sheet conformation characteristic of fibrils. Overall, these results led us to conclude that calcium ions stimulate the formation of oligomers of Aβ(1–40), that have been implicated in the pathogenesis of AD. |
format |
Text |
author |
Itkin, Anna Dupres, Vincent Dufrêne, Yves F. Bechinger, Burkhard Ruysschaert, Jean-Marie Raussens, Vincent |
author_facet |
Itkin, Anna Dupres, Vincent Dufrêne, Yves F. Bechinger, Burkhard Ruysschaert, Jean-Marie Raussens, Vincent |
author_sort |
Itkin, Anna |
title |
Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease |
title_short |
Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease |
title_full |
Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease |
title_fullStr |
Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease |
title_full_unstemmed |
Calcium Ions Promote Formation of Amyloid β-Peptide (1–40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease |
title_sort |
calcium ions promote formation of amyloid β-peptide (1–40) oligomers causally implicated in neuronal toxicity of alzheimer's disease |
publisher |
Public Library of Science |
publishDate |
2011 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065491 http://www.ncbi.nlm.nih.gov/pubmed/21464905 https://doi.org/10.1371/journal.pone.0018250 |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065491 http://www.ncbi.nlm.nih.gov/pubmed/21464905 http://dx.doi.org/10.1371/journal.pone.0018250 |
op_rights |
Itkin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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CC-BY |
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https://doi.org/10.1371/journal.pone.0018250 |
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e18250 |
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