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Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila.
Int J Mol Sci, 22(21).
Parkinson's disease (PD) is characterized by the progressive accumulation ofneuronal intracellular aggregates largely composed of alpha-Synuclein (αSyn)protein. The process of αSyn aggregation is induced during aging and enhanced byenvironmental stresses, such as the exposure to pesticides. Paraquat (PQ) is anherbicide which has been widely used in agriculture and associated with PD. PQ isknown to cause an increased oxidative stress in exposed individuals but theconsequences of such stress on αSyn conformation remains poorly understood. To studyαSyn pathogenic modifications in response to PQ, we exposed Drosophila expressinghuman αSyn to a chronic PQ protocol. We first showed that PQ exposure and αSynexpression synergistically induced fly mortality. The exposure to PQ was alsoassociated with increased levels of total and phosphorylated forms of αSyn in theDrosophila brain. Interestingly, PQ increased the detection of soluble αSyn inhighly denaturating buffer but did not increase αSyn resistance to proteinase Kdigestion. These results suggest that PQ induces the accumulation of toxic solubleand misfolded forms of αSyn but that these toxic forms do not form fibrils oraggregates that are detected by the proteinase K assay. Collectively, our resultsdemonstrate that Drosophila can be used to study the effect of PQ or otherenvironmental neurotoxins on αSyn driven pathology.
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