A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.

Amyloid beta (Aβ) peptides produced by APP cleavage are central to the pathology of Alzheimer's disease. Despite widespread interest in this issue, the relationship between the auto-assembly and toxicity of these peptides remains controversial. One intriguing feature stems from their capacity t...

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Autores principales:	Hélène Vignaud, Claude Bobo, Ioan Lascu, Karin Margareta Sörgjerd, Tamotsu Zako, Mizuo Maeda, Benedicte Salin, Sophie Lecomte, Christophe Cullin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f23dfafdfd8141d4960d7c5990229ebb
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spelling	oai:doaj.org-article:f23dfafdfd8141d4960d7c5990229ebb2021-11-18T08:47:18ZA structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.1932-620310.1371/journal.pone.0080262https://doaj.org/article/f23dfafdfd8141d4960d7c5990229ebb2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244667/?tool=EBIhttps://doaj.org/toc/1932-6203Amyloid beta (Aβ) peptides produced by APP cleavage are central to the pathology of Alzheimer's disease. Despite widespread interest in this issue, the relationship between the auto-assembly and toxicity of these peptides remains controversial. One intriguing feature stems from their capacity to form anti-parallel ß-sheet oligomeric intermediates that can be converted into a parallel topology to allow the formation of protofibrillar and fibrillar Aβ. Here, we present a novel approach to determining the molecular aspects of Aß assembly that is responsible for its in vivo toxicity. We selected Aß mutants with varying intracellular toxicities. In vitro, only toxic Aß (including wild-type Aß42) formed urea-resistant oligomers. These oligomers were able to assemble into fibrils that are rich in anti-parallel ß-sheet structures. Our results support the existence of a new pathway that depends on the folding capacity of Aß .Hélène VignaudClaude BoboIoan LascuKarin Margareta SörgjerdTamotsu ZakoMizuo MaedaBenedicte SalinSophie LecomteChristophe CullinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e80262 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hélène Vignaud Claude Bobo Ioan Lascu Karin Margareta Sörgjerd Tamotsu Zako Mizuo Maeda Benedicte Salin Sophie Lecomte Christophe Cullin A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.
description	Amyloid beta (Aβ) peptides produced by APP cleavage are central to the pathology of Alzheimer's disease. Despite widespread interest in this issue, the relationship between the auto-assembly and toxicity of these peptides remains controversial. One intriguing feature stems from their capacity to form anti-parallel ß-sheet oligomeric intermediates that can be converted into a parallel topology to allow the formation of protofibrillar and fibrillar Aβ. Here, we present a novel approach to determining the molecular aspects of Aß assembly that is responsible for its in vivo toxicity. We selected Aß mutants with varying intracellular toxicities. In vitro, only toxic Aß (including wild-type Aß42) formed urea-resistant oligomers. These oligomers were able to assemble into fibrils that are rich in anti-parallel ß-sheet structures. Our results support the existence of a new pathway that depends on the folding capacity of Aß .
format	article
author	Hélène Vignaud Claude Bobo Ioan Lascu Karin Margareta Sörgjerd Tamotsu Zako Mizuo Maeda Benedicte Salin Sophie Lecomte Christophe Cullin
author_facet	Hélène Vignaud Claude Bobo Ioan Lascu Karin Margareta Sörgjerd Tamotsu Zako Mizuo Maeda Benedicte Salin Sophie Lecomte Christophe Cullin
author_sort	Hélène Vignaud
title	A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.
title_short	A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.
title_full	A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.
title_fullStr	A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.
title_full_unstemmed	A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.
title_sort	structure-toxicity study of aß42 reveals a new anti-parallel aggregation pathway.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f23dfafdfd8141d4960d7c5990229ebb
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A structure-toxicity study of Aß42 reveals a new anti-parallel aggregation pathway.

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