Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria

Hongqun Ding, Yuyun Xiong, Jing Sun, Chen Chen, Jing Gao, Huaxi Xu
<span title="2018-06-28">2018</span> <i title="Frontiers Media SA"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/wrk3kouosrhcxiprcbguskdipu" style="color: black;">Frontiers in Neuroscience</a> </i> &nbsp;
The association of α-synuclein (α-syn) with mitochondria occurs through interaction with mitochondrial complex I. Defects in this protein have been linked to the pathogenesis of Parkinson disease (PD). Overexpression of α-synuclein in cells has been suggested to cause elevations in mitochondrial oxidant radicals and structural and functional abnormalities in mitochondria. Asiatic acid (AA), a triterpenoid, is an antioxidant that is used for depression, and we have shown that pretreatment with
more &raquo; ... can prevent PD-like damage, but its therapeutic effects in PD and mechanism remain unknown. In this study, we found that 0.5-2 mg AA/100 g diet significantly improves climbing ability in drosophila and extends their life-span-effects that we attributed to its antioxidant properties. AA also protected mitochondria against oxidative stress and apoptosis in a rotenone-induced cellular model. In an isolated mitochondria model, AA attenuated the decline in mitochondrial membrane potential that was induced by α-syn. Consequently, AA maintained membrane integrity and ATP production. Finally, we demonstrated that AA protects by blocking the translocation of α-syn into mitochondria. Our results suggest that mitochondria are crucial in PD and that AA is an excellent candidate for the prevention and therapy of this disease.
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