(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-sy...

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Autores principales:	Joana Angélica Loureiro, Stéphanie Andrade, Lies Goderis, Ruben Gomez-Gutierrez, Claudio Soto, Rodrigo Morales, Maria Carmo Pereira
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	α-synuclein protein aggregation Parkinson’s disease protein secondary structure aggregation mechanisms Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/be84e67481704ce9a33c5fc43ea2cda7
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spelling	oai:doaj.org-article:be84e67481704ce9a33c5fc43ea2cda72021-11-25T17:57:22Z(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants10.3390/ijms2222125091422-00671661-6596https://doaj.org/article/be84e67481704ce9a33c5fc43ea2cda72021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12509https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Parkinson’s disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-synuclein can assume conformations rich in either α-helix or β-sheets. The mechanisms of α-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that β-sheet conformation of α-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of α-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl β-D-glucopyranoside (OG). The effect of surfactants in α-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The α-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that β-sheet structures comprise the assembly of the fibrils.Joana Angélica LoureiroStéphanie AndradeLies GoderisRuben Gomez-GutierrezClaudio SotoRodrigo MoralesMaria Carmo PereiraMDPI AGarticleα-synucleinprotein aggregationParkinson’s diseaseprotein secondary structureaggregation mechanismsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12509, p 12509 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	α-synuclein protein aggregation Parkinson’s disease protein secondary structure aggregation mechanisms Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	α-synuclein protein aggregation Parkinson’s disease protein secondary structure aggregation mechanisms Biology (General) QH301-705.5 Chemistry QD1-999 Joana Angélica Loureiro Stéphanie Andrade Lies Goderis Ruben Gomez-Gutierrez Claudio Soto Rodrigo Morales Maria Carmo Pereira (De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants
description	Parkinson’s disease (PD) is the second most common neurodegenerative disorder. An important hallmark of PD involves the pathological aggregation of proteins in structures known as Lewy bodies. The major component of these proteinaceous inclusions is alpha (α)-synuclein. In different conditions, α-synuclein can assume conformations rich in either α-helix or β-sheets. The mechanisms of α-synuclein misfolding, aggregation, and fibrillation remain unknown, but it is thought that β-sheet conformation of α-synuclein is responsible for its associated toxic mechanisms. To gain fundamental insights into the process of α-synuclein misfolding and aggregation, the secondary structure of this protein in the presence of charged and non-charged surfactant solutions was characterized. The selected surfactants were (anionic) sodium dodecyl sulphate (SDS), (cationic) cetyltrimethylammonium chloride (CTAC), and (uncharged) octyl β-D-glucopyranoside (OG). The effect of surfactants in α-synuclein misfolding was assessed by ultra-structural analyses, in vitro aggregation assays, and secondary structure analyses. The α-synuclein aggregation in the presence of negatively charged SDS suggests that SDS-monomer complexes stimulate the aggregation process. A reduction in the electrostatic repulsion between N- and C-terminal and in the hydrophobic interactions between the NAC (non-amyloid beta component) region and the C-terminal seems to be important to undergo aggregation. Fourier transform infrared spectroscopy (FTIR) measurements show that β-sheet structures comprise the assembly of the fibrils.
format	article
author	Joana Angélica Loureiro Stéphanie Andrade Lies Goderis Ruben Gomez-Gutierrez Claudio Soto Rodrigo Morales Maria Carmo Pereira
author_facet	Joana Angélica Loureiro Stéphanie Andrade Lies Goderis Ruben Gomez-Gutierrez Claudio Soto Rodrigo Morales Maria Carmo Pereira
author_sort	Joana Angélica Loureiro
title	(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants
title_short	(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants
title_full	(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants
title_fullStr	(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants
title_full_unstemmed	(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants
title_sort	(de)stabilization of alpha-synuclein fibrillary aggregation by charged and uncharged surfactants
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/be84e67481704ce9a33c5fc43ea2cda7
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(De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants

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