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Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies

The accumulation of amyloid fibrils is the hallmark of several major human diseases. Although the formation of these supramolecular entities has previously been associated with proteins and peptides, it was later demonstrated that even phenylalanine, a single amino acid, can form fibrils that have a...

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Autores principales: Shaham-Niv, Shira, Adler-Abramovich, Lihi, Schnaider, Lee, Gazit, Ehud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643800/
https://www.ncbi.nlm.nih.gov/pubmed/26601224
http://dx.doi.org/10.1126/sciadv.1500137
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author Shaham-Niv, Shira
Adler-Abramovich, Lihi
Schnaider, Lee
Gazit, Ehud
author_facet Shaham-Niv, Shira
Adler-Abramovich, Lihi
Schnaider, Lee
Gazit, Ehud
author_sort Shaham-Niv, Shira
collection PubMed
description The accumulation of amyloid fibrils is the hallmark of several major human diseases. Although the formation of these supramolecular entities has previously been associated with proteins and peptides, it was later demonstrated that even phenylalanine, a single amino acid, can form fibrils that have amyloid-like biophysical, biochemical, and cytotoxic properties. Moreover, the generation of antibodies against these assemblies in phenylketonuria patients and the correlating mice model suggested a pathological role for the assemblies. We determine that several other metabolites that accumulate in metabolic disorders form ordered amyloid-like ultrastructures, which induce apoptotic cell death, as observed for amyloid structures. The formation of amyloid-like assemblies by metabolites implies a general phenomenon of amyloid formation, not limited to proteins and peptides, and offers a new paradigm for metabolic diseases.
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spelling pubmed-46438002015-11-23 Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies Shaham-Niv, Shira Adler-Abramovich, Lihi Schnaider, Lee Gazit, Ehud Sci Adv Research Articles The accumulation of amyloid fibrils is the hallmark of several major human diseases. Although the formation of these supramolecular entities has previously been associated with proteins and peptides, it was later demonstrated that even phenylalanine, a single amino acid, can form fibrils that have amyloid-like biophysical, biochemical, and cytotoxic properties. Moreover, the generation of antibodies against these assemblies in phenylketonuria patients and the correlating mice model suggested a pathological role for the assemblies. We determine that several other metabolites that accumulate in metabolic disorders form ordered amyloid-like ultrastructures, which induce apoptotic cell death, as observed for amyloid structures. The formation of amyloid-like assemblies by metabolites implies a general phenomenon of amyloid formation, not limited to proteins and peptides, and offers a new paradigm for metabolic diseases. American Association for the Advancement of Science 2015-08-14 /pmc/articles/PMC4643800/ /pubmed/26601224 http://dx.doi.org/10.1126/sciadv.1500137 Text en Copyright © 2015, The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Shaham-Niv, Shira
Adler-Abramovich, Lihi
Schnaider, Lee
Gazit, Ehud
Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies
title Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies
title_full Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies
title_fullStr Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies
title_full_unstemmed Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies
title_short Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies
title_sort extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643800/
https://www.ncbi.nlm.nih.gov/pubmed/26601224
http://dx.doi.org/10.1126/sciadv.1500137
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