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The Role of Glycation on the Aggregation Properties of IAPP

Epidemiological evidence shows an increased risk for developing Alzheimer’s disease in people affected by diabetes, a pathology associated with increased hyperglycemia. A potential factor that could explain this link could be the role that sugars may play in both diseases under the form of glycation...

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Autores principales: Milordini, Giulia, Zacco, Elsa, Percival, Matthew, Puglisi, Rita, Dal Piaz, Fabrizio, Temussi, Pierandrea, Pastore, Annalisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284065/
https://www.ncbi.nlm.nih.gov/pubmed/32582762
http://dx.doi.org/10.3389/fmolb.2020.00104
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author Milordini, Giulia
Zacco, Elsa
Percival, Matthew
Puglisi, Rita
Dal Piaz, Fabrizio
Temussi, Pierandrea
Pastore, Annalisa
author_facet Milordini, Giulia
Zacco, Elsa
Percival, Matthew
Puglisi, Rita
Dal Piaz, Fabrizio
Temussi, Pierandrea
Pastore, Annalisa
author_sort Milordini, Giulia
collection PubMed
description Epidemiological evidence shows an increased risk for developing Alzheimer’s disease in people affected by diabetes, a pathology associated with increased hyperglycemia. A potential factor that could explain this link could be the role that sugars may play in both diseases under the form of glycation. Contrary to glycosylation, glycation is an enzyme-free reaction that leads to formation of toxic advanced glycation end-products (AGEs). In diabetes, the islet amyloid polypeptide (IAPP or amylin) is found to be heavily glycated and to form toxic amyloid-like aggregates, similar to those observed for the Aβ peptides, often also heavily glycated, observed in Alzheimer patients. Here, we studied the effects of glycation on the structure and aggregation properties of IAPP with several biophysical techniques ranging from fluorescence to circular dichroism, mass spectrometry and atomic force microscopy. We demonstrate that glycation occurs exclusively on the N-terminal lysine leaving the only arginine (Arg11) unmodified. At variance with recent studies, we show that the dynamical interplay between glycation and aggregation affects the structure of the peptide, slows down the aggregation process and influences the aggregate morphology.
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spelling pubmed-72840652020-06-23 The Role of Glycation on the Aggregation Properties of IAPP Milordini, Giulia Zacco, Elsa Percival, Matthew Puglisi, Rita Dal Piaz, Fabrizio Temussi, Pierandrea Pastore, Annalisa Front Mol Biosci Molecular Biosciences Epidemiological evidence shows an increased risk for developing Alzheimer’s disease in people affected by diabetes, a pathology associated with increased hyperglycemia. A potential factor that could explain this link could be the role that sugars may play in both diseases under the form of glycation. Contrary to glycosylation, glycation is an enzyme-free reaction that leads to formation of toxic advanced glycation end-products (AGEs). In diabetes, the islet amyloid polypeptide (IAPP or amylin) is found to be heavily glycated and to form toxic amyloid-like aggregates, similar to those observed for the Aβ peptides, often also heavily glycated, observed in Alzheimer patients. Here, we studied the effects of glycation on the structure and aggregation properties of IAPP with several biophysical techniques ranging from fluorescence to circular dichroism, mass spectrometry and atomic force microscopy. We demonstrate that glycation occurs exclusively on the N-terminal lysine leaving the only arginine (Arg11) unmodified. At variance with recent studies, we show that the dynamical interplay between glycation and aggregation affects the structure of the peptide, slows down the aggregation process and influences the aggregate morphology. Frontiers Media S.A. 2020-06-03 /pmc/articles/PMC7284065/ /pubmed/32582762 http://dx.doi.org/10.3389/fmolb.2020.00104 Text en Copyright © 2020 Milordini, Zacco, Percival, Puglisi, Dal Piaz, Temussi and Pastore. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Milordini, Giulia
Zacco, Elsa
Percival, Matthew
Puglisi, Rita
Dal Piaz, Fabrizio
Temussi, Pierandrea
Pastore, Annalisa
The Role of Glycation on the Aggregation Properties of IAPP
title The Role of Glycation on the Aggregation Properties of IAPP
title_full The Role of Glycation on the Aggregation Properties of IAPP
title_fullStr The Role of Glycation on the Aggregation Properties of IAPP
title_full_unstemmed The Role of Glycation on the Aggregation Properties of IAPP
title_short The Role of Glycation on the Aggregation Properties of IAPP
title_sort role of glycation on the aggregation properties of iapp
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284065/
https://www.ncbi.nlm.nih.gov/pubmed/32582762
http://dx.doi.org/10.3389/fmolb.2020.00104
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