Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>

Parkinson’s disease (PD) is characterized by the progressive accumulation of neuronal intracellular aggregates largely composed of alpha-Synuclein (αSyn) protein. The process of αSyn aggregation is induced during aging and enhanced by environmental stresses, such as the exposure to pesticides. Paraq...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jean-Noël Arsac, Marianne Sedru, Mireille Dartiguelongue, Johann Vulin, Nathalie Davoust, Thierry Baron, Bertrand Mollereau
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Parkinson’s disease alpha-synuclein <i>Drosophila</i> paraquat Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/de6abadb31e94cb88f49961502f213bc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:de6abadb31e94cb88f49961502f213bc
record_format	dspace
spelling	oai:doaj.org-article:de6abadb31e94cb88f49961502f213bc2021-11-11T17:05:33ZChronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>10.3390/ijms2221116131422-00671661-6596https://doaj.org/article/de6abadb31e94cb88f49961502f213bc2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11613https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Parkinson’s disease (PD) is characterized by the progressive accumulation of neuronal intracellular aggregates largely composed of alpha-Synuclein (αSyn) protein. The process of αSyn aggregation is induced during aging and enhanced by environmental stresses, such as the exposure to pesticides. Paraquat (PQ) is an herbicide which has been widely used in agriculture and associated with PD. PQ is known to cause an increased oxidative stress in exposed individuals but the consequences of such stress on αSyn conformation remains poorly understood. To study αSyn pathogenic modifications in response to PQ, we exposed <i>Drosophila</i> expressing human αSyn to a chronic PQ protocol. We first showed that PQ exposure and αSyn expression synergistically induced fly mortality. The exposure to PQ was also associated with increased levels of total and phosphorylated forms of αSyn in the <i>Drosophila</i> brain. Interestingly, PQ increased the detection of soluble αSyn in highly denaturating buffer but did not increase αSyn resistance to proteinase K digestion. These results suggest that PQ induces the accumulation of toxic soluble and misfolded forms of αSyn but that these toxic forms do not form fibrils or aggregates that are detected by the proteinase K assay. Collectively, our results demonstrate that <i>Drosophila</i> can be used to study the effect of PQ or other environmental neurotoxins on αSyn driven pathology.Jean-Noël ArsacMarianne SedruMireille DartiguelongueJohann VulinNathalie DavoustThierry BaronBertrand MollereauMDPI AGarticleParkinson’s diseasealpha-synuclein<i>Drosophila</i>paraquatBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11613, p 11613 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Parkinson’s disease alpha-synuclein <i>Drosophila</i> paraquat Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Parkinson’s disease alpha-synuclein <i>Drosophila</i> paraquat Biology (General) QH301-705.5 Chemistry QD1-999 Jean-Noël Arsac Marianne Sedru Mireille Dartiguelongue Johann Vulin Nathalie Davoust Thierry Baron Bertrand Mollereau Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>
description	Parkinson’s disease (PD) is characterized by the progressive accumulation of neuronal intracellular aggregates largely composed of alpha-Synuclein (αSyn) protein. The process of αSyn aggregation is induced during aging and enhanced by environmental stresses, such as the exposure to pesticides. Paraquat (PQ) is an herbicide which has been widely used in agriculture and associated with PD. PQ is known to cause an increased oxidative stress in exposed individuals but the consequences of such stress on αSyn conformation remains poorly understood. To study αSyn pathogenic modifications in response to PQ, we exposed <i>Drosophila</i> expressing human αSyn to a chronic PQ protocol. We first showed that PQ exposure and αSyn expression synergistically induced fly mortality. The exposure to PQ was also associated with increased levels of total and phosphorylated forms of αSyn in the <i>Drosophila</i> brain. Interestingly, PQ increased the detection of soluble αSyn in highly denaturating buffer but did not increase αSyn resistance to proteinase K digestion. These results suggest that PQ induces the accumulation of toxic soluble and misfolded forms of αSyn but that these toxic forms do not form fibrils or aggregates that are detected by the proteinase K assay. Collectively, our results demonstrate that <i>Drosophila</i> can be used to study the effect of PQ or other environmental neurotoxins on αSyn driven pathology.
format	article
author	Jean-Noël Arsac Marianne Sedru Mireille Dartiguelongue Johann Vulin Nathalie Davoust Thierry Baron Bertrand Mollereau
author_facet	Jean-Noël Arsac Marianne Sedru Mireille Dartiguelongue Johann Vulin Nathalie Davoust Thierry Baron Bertrand Mollereau
author_sort	Jean-Noël Arsac
title	Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>
title_short	Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>
title_full	Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>
title_fullStr	Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>
title_full_unstemmed	Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>
title_sort	chronic exposure to paraquat induces alpha-synuclein pathogenic modifications in <i>drosophila</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/de6abadb31e94cb88f49961502f213bc
work_keys_str_mv	AT jeannoelarsac chronicexposuretoparaquatinducesalphasynucleinpathogenicmodificationsinidrosophilai AT mariannesedru chronicexposuretoparaquatinducesalphasynucleinpathogenicmodificationsinidrosophilai AT mireilledartiguelongue chronicexposuretoparaquatinducesalphasynucleinpathogenicmodificationsinidrosophilai AT johannvulin chronicexposuretoparaquatinducesalphasynucleinpathogenicmodificationsinidrosophilai AT nathaliedavoust chronicexposuretoparaquatinducesalphasynucleinpathogenicmodificationsinidrosophilai AT thierrybaron chronicexposuretoparaquatinducesalphasynucleinpathogenicmodificationsinidrosophilai AT bertrandmollereau chronicexposuretoparaquatinducesalphasynucleinpathogenicmodificationsinidrosophilai
_version_	1718432207930916864

Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in <i>Drosophila</i>

Ejemplares similares