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Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila

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...

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Autores principales: Arsac, Jean-Noël, Sedru, Marianne, Dartiguelongue, Mireille, Vulin, Johann, Davoust, Nathalie, Baron, Thierry, Mollereau, Bertrand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584077/
https://www.ncbi.nlm.nih.gov/pubmed/34769043
http://dx.doi.org/10.3390/ijms222111613
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author Arsac, Jean-Noël
Sedru, Marianne
Dartiguelongue, Mireille
Vulin, Johann
Davoust, Nathalie
Baron, Thierry
Mollereau, Bertrand
author_facet Arsac, Jean-Noël
Sedru, Marianne
Dartiguelongue, Mireille
Vulin, Johann
Davoust, Nathalie
Baron, Thierry
Mollereau, Bertrand
author_sort Arsac, Jean-Noël
collection PubMed
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 Drosophila 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 Drosophila 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 Drosophila can be used to study the effect of PQ or other environmental neurotoxins on αSyn driven pathology.
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spelling pubmed-85840772021-11-12 Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila Arsac, Jean-Noël Sedru, Marianne Dartiguelongue, Mireille Vulin, Johann Davoust, Nathalie Baron, Thierry Mollereau, Bertrand Int J Mol Sci Article 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 Drosophila 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 Drosophila 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 Drosophila can be used to study the effect of PQ or other environmental neurotoxins on αSyn driven pathology. MDPI 2021-10-27 /pmc/articles/PMC8584077/ /pubmed/34769043 http://dx.doi.org/10.3390/ijms222111613 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arsac, Jean-Noël
Sedru, Marianne
Dartiguelongue, Mireille
Vulin, Johann
Davoust, Nathalie
Baron, Thierry
Mollereau, Bertrand
Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila
title Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila
title_full Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila
title_fullStr Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila
title_full_unstemmed Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila
title_short Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila
title_sort chronic exposure to paraquat induces alpha-synuclein pathogenic modifications in drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584077/
https://www.ncbi.nlm.nih.gov/pubmed/34769043
http://dx.doi.org/10.3390/ijms222111613
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