Cargando…

The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity

Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tiss...

Descripción completa

Detalles Bibliográficos
Autores principales: Iannuzzi, Clara, Irace, Gaetano, Sirangelo, Ivana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272481/
https://www.ncbi.nlm.nih.gov/pubmed/25648594
http://dx.doi.org/10.3390/molecules20022510
_version_ 1783377166698807296
author Iannuzzi, Clara
Irace, Gaetano
Sirangelo, Ivana
author_facet Iannuzzi, Clara
Irace, Gaetano
Sirangelo, Ivana
author_sort Iannuzzi, Clara
collection PubMed
description Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid diseases. Experimental evidence indicate that they can play an active role in favoring amyloid fibril formation and stabilization. Binding of GAGs to amyloid fibrils occurs mainly through electrostatic interactions involving the negative polyelectrolyte charges and positively charged side chains residues of aggregating protein. Similarly to catalyst for reactions, GAGs favor aggregation, nucleation and amyloid fibril formation functioning as a structural templates for the self-assembly of highly cytotoxic oligomeric precursors, rich in β-sheets, into harmless amyloid fibrils. Moreover, the GAGs amyloid promoting activity can be facilitated through specific interactions via consensus binding sites between amyloid polypeptide and GAGs molecules. We review the effect of GAGs on amyloid deposition as well as proteins not strictly related to diseases. In addition, we consider the potential of the GAGs therapy in amyloidosis.
format Online
Article
Text
id pubmed-6272481
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62724812018-12-13 The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity Iannuzzi, Clara Irace, Gaetano Sirangelo, Ivana Molecules Review Amyloidosis is a protein folding disorder in which normally soluble proteins are deposited extracellularly as insoluble fibrils, impairing tissue structure and function. Charged polyelectrolytes such as glycosaminoglycans (GAGs) are frequently found associated with the proteinaceous deposits in tissues of patients affected by amyloid diseases. Experimental evidence indicate that they can play an active role in favoring amyloid fibril formation and stabilization. Binding of GAGs to amyloid fibrils occurs mainly through electrostatic interactions involving the negative polyelectrolyte charges and positively charged side chains residues of aggregating protein. Similarly to catalyst for reactions, GAGs favor aggregation, nucleation and amyloid fibril formation functioning as a structural templates for the self-assembly of highly cytotoxic oligomeric precursors, rich in β-sheets, into harmless amyloid fibrils. Moreover, the GAGs amyloid promoting activity can be facilitated through specific interactions via consensus binding sites between amyloid polypeptide and GAGs molecules. We review the effect of GAGs on amyloid deposition as well as proteins not strictly related to diseases. In addition, we consider the potential of the GAGs therapy in amyloidosis. MDPI 2015-02-02 /pmc/articles/PMC6272481/ /pubmed/25648594 http://dx.doi.org/10.3390/molecules20022510 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Iannuzzi, Clara
Irace, Gaetano
Sirangelo, Ivana
The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
title The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
title_full The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
title_fullStr The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
title_full_unstemmed The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
title_short The Effect of Glycosaminoglycans (GAGs) on Amyloid Aggregation and Toxicity
title_sort effect of glycosaminoglycans (gags) on amyloid aggregation and toxicity
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272481/
https://www.ncbi.nlm.nih.gov/pubmed/25648594
http://dx.doi.org/10.3390/molecules20022510
work_keys_str_mv AT iannuzziclara theeffectofglycosaminoglycansgagsonamyloidaggregationandtoxicity
AT iracegaetano theeffectofglycosaminoglycansgagsonamyloidaggregationandtoxicity
AT sirangeloivana theeffectofglycosaminoglycansgagsonamyloidaggregationandtoxicity
AT iannuzziclara effectofglycosaminoglycansgagsonamyloidaggregationandtoxicity
AT iracegaetano effectofglycosaminoglycansgagsonamyloidaggregationandtoxicity
AT sirangeloivana effectofglycosaminoglycansgagsonamyloidaggregationandtoxicity