α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice

Abstract Type 2 diabetes (T2D), alike Parkinson’s disease (PD), belongs to the group of protein misfolding diseases (PMDs), which share aggregation of misfolded proteins as a hallmark. Although the major aggregating peptide in β-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synucl...

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Autores principales:	Marija Mucibabic, Pär Steneberg, Emmelie Lidh, Jurate Straseviciene, Agnieszka Ziolkowska, Ulf Dahl, Emma Lindahl, Helena Edlund
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c38137531696423c9b543012d50e5640
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spelling	oai:doaj.org-article:c38137531696423c9b543012d50e56402021-12-02T16:08:55Zα-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice10.1038/s41598-020-77409-z2045-2322https://doaj.org/article/c38137531696423c9b543012d50e56402020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77409-zhttps://doaj.org/toc/2045-2322Abstract Type 2 diabetes (T2D), alike Parkinson’s disease (PD), belongs to the group of protein misfolding diseases (PMDs), which share aggregation of misfolded proteins as a hallmark. Although the major aggregating peptide in β-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synuclein (αSyn), the aggregating peptide in substantia nigra neurons of PD patients, is expressed also in β-cells. Here we show that αSyn, encoded by Snca, is a component of amyloid extracted from pancreas of transgenic mice overexpressing human IAPP (denoted hIAPPtg mice) and from islets of T2D individuals. Notably, αSyn dose-dependently promoted IAPP fibril formation in vitro and tail-vein injection of αSyn in hIAPPtg mice enhanced β-cell amyloid formation in vivo whereas β-cell amyloid formation was reduced in hIAPPtg mice on a Snca −/− background. Taken together, our findings provide evidence that αSyn and IAPP co-aggregate both in vitro and in vivo, suggesting a role for αSyn in β-cell amyloid formation.Marija MucibabicPär StenebergEmmelie LidhJurate StrasevicieneAgnieszka ZiolkowskaUlf DahlEmma LindahlHelena EdlundNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marija Mucibabic Pär Steneberg Emmelie Lidh Jurate Straseviciene Agnieszka Ziolkowska Ulf Dahl Emma Lindahl Helena Edlund α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice
description	Abstract Type 2 diabetes (T2D), alike Parkinson’s disease (PD), belongs to the group of protein misfolding diseases (PMDs), which share aggregation of misfolded proteins as a hallmark. Although the major aggregating peptide in β-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synuclein (αSyn), the aggregating peptide in substantia nigra neurons of PD patients, is expressed also in β-cells. Here we show that αSyn, encoded by Snca, is a component of amyloid extracted from pancreas of transgenic mice overexpressing human IAPP (denoted hIAPPtg mice) and from islets of T2D individuals. Notably, αSyn dose-dependently promoted IAPP fibril formation in vitro and tail-vein injection of αSyn in hIAPPtg mice enhanced β-cell amyloid formation in vivo whereas β-cell amyloid formation was reduced in hIAPPtg mice on a Snca −/− background. Taken together, our findings provide evidence that αSyn and IAPP co-aggregate both in vitro and in vivo, suggesting a role for αSyn in β-cell amyloid formation.
format	article
author	Marija Mucibabic Pär Steneberg Emmelie Lidh Jurate Straseviciene Agnieszka Ziolkowska Ulf Dahl Emma Lindahl Helena Edlund
author_facet	Marija Mucibabic Pär Steneberg Emmelie Lidh Jurate Straseviciene Agnieszka Ziolkowska Ulf Dahl Emma Lindahl Helena Edlund
author_sort	Marija Mucibabic
title	α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice
title_short	α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice
title_full	α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice
title_fullStr	α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice
title_full_unstemmed	α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice
title_sort	α-synuclein promotes iapp fibril formation in vitro and β-cell amyloid formation in vivo in mice
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/c38137531696423c9b543012d50e5640
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α-Synuclein promotes IAPP fibril formation in vitro and β-cell amyloid formation in vivo in mice

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