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="" 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.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.3389/fnins.2018.00431</a> <a target="_blank" rel="external noopener" href="">pmid:30002614</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC6031891</a> <a target="_blank" rel="external noopener" href="">fatcat:qabh3qm3lnhhhl5skhnhnfbvp4</a> </span>
<a target="_blank" rel="noopener" href="" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href=""> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> </button> </a> <a target="_blank" rel="external noopener" href="" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> </button> </a>