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

Frontiers in Neuroscience
Hongqun DingHuaxi Xu

Abstract

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 AA 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 tha...Continue Reading

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Citations

Sep 26, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yiming HanZhengfang Yi
Nov 11, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Da Hye SongJeung Hee An
Jun 23, 2020·Oxidative Medicine and Cellular Longevity·Kecheng LeiLingjing Jin
Jul 8, 2020·Antioxidants·Han-A Park, Amy C Ellis
Oct 27, 2020·Oxidative Medicine and Cellular Longevity·Sandro PercárioMaria Fani Dolabela

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Methods Mentioned

BETA
Assay
MDA
transgenic
fluorescence microscopy

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis