Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria
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 oxi...
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00431/full |
| _version_ | 1818151719279788032 |
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| author | Hongqun Ding Yuyun Xiong Jing Sun Chen Chen Jing Gao Huaxi Xu |
| author_facet | Hongqun Ding Yuyun Xiong Jing Sun Chen Chen Jing Gao Huaxi Xu |
| author_sort | Hongqun Ding |
| collection | DOAJ |
| description | 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 that AA is an excellent candidate for the prevention and therapy of this disease. |
| first_indexed | 2024-12-11T13:43:17Z |
| format | Article |
| id | doaj.art-80892c966af54651b94ba9fdd5618eb7 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-11T13:43:17Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-80892c966af54651b94ba9fdd5618eb72022-12-22T01:04:40ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-06-011210.3389/fnins.2018.00431354837Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into MitochondriaHongqun Ding0Yuyun Xiong1Jing Sun2Chen Chen3Jing Gao4Huaxi Xu5Department of Clinical Laboratory Diagnostics, School of Medicine, Jiangsu University, Zhenjiang, ChinaDepartment of Clinical Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Medicinal Pharmacy, School of Pharmacy, Jiangsu University, Zhenjiang, ChinaDepartment of Medicinal Pharmacy, School of Pharmacy, Jiangsu University, Zhenjiang, ChinaDepartment of Medicinal Pharmacy, School of Pharmacy, Jiangsu University, Zhenjiang, ChinaDepartment of Clinical Laboratory Diagnostics, School of Medicine, Jiangsu University, Zhenjiang, ChinaThe 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 that AA is an excellent candidate for the prevention and therapy of this disease.https://www.frontiersin.org/article/10.3389/fnins.2018.00431/fullα-synucleinmitochondrionapoptosisasiatic acidParkinson disease |
| spellingShingle | Hongqun Ding Yuyun Xiong Jing Sun Chen Chen Jing Gao Huaxi Xu Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria Frontiers in Neuroscience α-synuclein mitochondrion apoptosis asiatic acid Parkinson disease |
| title | Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria |
| title_full | Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria |
| title_fullStr | Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria |
| title_full_unstemmed | Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria |
| title_short | Asiatic Acid Prevents Oxidative Stress and Apoptosis by Inhibiting the Translocation of α-Synuclein Into Mitochondria |
| title_sort | asiatic acid prevents oxidative stress and apoptosis by inhibiting the translocation of α synuclein into mitochondria |
| topic | α-synuclein mitochondrion apoptosis asiatic acid Parkinson disease |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00431/full |
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