Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils

Abstract Amyloidogenic protein assembly into insoluble fibrillar aggregates is linked with several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, affecting millions of people worldwide. The search for a potential anti-amyloid drug has led to the discovery of hundreds of com...

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Autores principales:	Andrius Sakalauskas, Mantas Ziaunys, Vytautas Smirnovas
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0651154ecfd040219a51e76802256ef8
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spelling	oai:doaj.org-article:0651154ecfd040219a51e76802256ef82021-12-02T19:04:11ZGallic acid oxidation products alter the formation pathway of insulin amyloid fibrils10.1038/s41598-020-70982-32045-2322https://doaj.org/article/0651154ecfd040219a51e76802256ef82020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-70982-3https://doaj.org/toc/2045-2322Abstract Amyloidogenic protein assembly into insoluble fibrillar aggregates is linked with several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, affecting millions of people worldwide. The search for a potential anti-amyloid drug has led to the discovery of hundreds of compounds, none of which have passed all clinical trials. Gallic acid has been shown to both modulate factors leading to the onset of neurodegenerative disorders, as well as directly inhibit amyloid formation. However, the conditions under which this effect is seen could lead to oxidation of this polyphenol, likely changing its properties. Here we examine the effect of gallic acid and its oxidised form on the aggregation of a model amyloidogenic protein–insulin at low pH conditions. We show a vastly higher inhibitory potential of the oxidised form, as well as an alteration in the aggregation pathway, leading to the formation of a specific fibril conformation.Andrius SakalauskasMantas ZiaunysVytautas SmirnovasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrius Sakalauskas Mantas Ziaunys Vytautas Smirnovas Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
description	Abstract Amyloidogenic protein assembly into insoluble fibrillar aggregates is linked with several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, affecting millions of people worldwide. The search for a potential anti-amyloid drug has led to the discovery of hundreds of compounds, none of which have passed all clinical trials. Gallic acid has been shown to both modulate factors leading to the onset of neurodegenerative disorders, as well as directly inhibit amyloid formation. However, the conditions under which this effect is seen could lead to oxidation of this polyphenol, likely changing its properties. Here we examine the effect of gallic acid and its oxidised form on the aggregation of a model amyloidogenic protein–insulin at low pH conditions. We show a vastly higher inhibitory potential of the oxidised form, as well as an alteration in the aggregation pathway, leading to the formation of a specific fibril conformation.
format	article
author	Andrius Sakalauskas Mantas Ziaunys Vytautas Smirnovas
author_facet	Andrius Sakalauskas Mantas Ziaunys Vytautas Smirnovas
author_sort	Andrius Sakalauskas
title	Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
title_short	Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
title_full	Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
title_fullStr	Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
title_full_unstemmed	Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
title_sort	gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0651154ecfd040219a51e76802256ef8
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Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils

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