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 Ca(2+) homeostasis in aging brains and in neurodegenerative disorders plays a crucial r...

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Autores principales:	Anna Itkin, Vincent Dupres, Yves F Dufrêne, Burkhard Bechinger, Jean-Marie Ruysschaert, Vincent Raussens
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/73560769eb2b4e0fbcf4cfe302884870
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spelling	oai:doaj.org-article:73560769eb2b4e0fbcf4cfe3028848702021-11-18T06:56:43ZCalcium ions promote formation of amyloid β-peptide (1-40) oligomers causally implicated in neuronal toxicity of Alzheimer's disease.1932-620310.1371/journal.pone.0018250https://doaj.org/article/73560769eb2b4e0fbcf4cfe3028848702011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21464905/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Amyloid 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 Ca(2+) 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 Ca(2+), Aβ(1-40) preferentially formed oligomers similar to those formed by Aβ(1-40)E22G with or without added Ca(2+), whereas in the absence of added Ca(2+) 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 Ca(2+), 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.Anna ItkinVincent DupresYves F DufrêneBurkhard BechingerJean-Marie RuysschaertVincent RaussensPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e18250 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Itkin Vincent Dupres Yves F Dufrêne Burkhard Bechinger Jean-Marie Ruysschaert Vincent Raussens Calcium ions promote formation of amyloid β-peptide (1-40) oligomers causally implicated in neuronal toxicity of Alzheimer's disease.
description	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 Ca(2+) 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 Ca(2+), Aβ(1-40) preferentially formed oligomers similar to those formed by Aβ(1-40)E22G with or without added Ca(2+), whereas in the absence of added Ca(2+) 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 Ca(2+), 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	article
author	Anna Itkin Vincent Dupres Yves F Dufrêne Burkhard Bechinger Jean-Marie Ruysschaert Vincent Raussens
author_facet	Anna Itkin Vincent Dupres Yves F Dufrêne Burkhard Bechinger Jean-Marie Ruysschaert Vincent Raussens
author_sort	Anna Itkin
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 (PLoS)
publishDate	2011
url	https://doaj.org/article/73560769eb2b4e0fbcf4cfe302884870
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Calcium ions promote formation of amyloid β-peptide (1-40) oligomers causally implicated in neuronal toxicity of Alzheimer's disease.

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