Oxidants Induce α-Synuclein-Independent Toxicity in a Fission Yeast Model for Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disease caused by the death of midbrain dopaminergic neurons. The misfolding and aggregation of the protein α-synuclein and accumulation of oxidants is thought to underlie the cell death, but how α-synuclein becomes toxic is unclear. Using fission yeast as a model organism, where α-synuclein expression induces aggregation but not toxicity, we tested the hypothesis that α-synuclein toxicity can result from the combination of protein aggregation and oxidative stress. Surprisingly, we found that both oxidants (hydrogen peroxide and cumene hydroperoxide) tested in our study resulted in α-synuclein-independent toxicity. Nevertheless, this work illustrates the usefulness of yeasts in evaluating genetic factors and environmental factors like oxidative stress to potentially regulate α-synuclein toxicity linked to Parkinson's disease.

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