Search

Mitochondrial dysfunction, oxidative stress, and α-synuclein oligomerization occur in Parkinson disease (PD). We used an in vitroPD cybrid approach that models these three phenomena specifically to evaluate the impact of mitochondria-derived oxidative stress on α-synuclein oligomerization. Compared with control cybrid cell lines, reactive oxygen species (ROS) production and protein oxidative stress markers were elevated in PD cybrids. The antioxidants CoQ10and GSH attenuated changes in PD cybrid peroxide, protein carbonyl, and protein sulfhydryl levels. Elevated PD cybrid α-synuclein oligomer levels were also attenuated by CoQ10and GSH. In PD cybrids, α-synuclein oligomerization was activated viaa complex I–mediated increase in the free tubulinpolymerized tubulin ratio. CoQ10but not GSH increased complex I activity, restored ATP to control levels, and normalized the PD cybrid free tubulinpolymerized tubulin ratio. Overall, we conclude that two different antioxidants can decrease α-synuclein oligomerization whether by improving mitochondrial function or by preventing protein carbonylation or both. We conclude that mitochondrial dysfunction can induce α-synuclein oligomerization viaATP depletion–driven microtubule depolymerization and viaROS increase–driven protein oxidation. [ABSTRACT FROM AUTHOR]