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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2015
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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. |
format | Online Article Text |
id | pubmed-4643800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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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