线粒体靶向抗氧化剂Mitoquinone和积雪草酸对朊病毒感染的神经细胞的治疗作用研究

The Therapeutic Role of Mitochondria-targeted Antioxidants Mitoquinone and Asiatic Acid in Scrapie Infected Cell Line SMB-S15

朊病毒病(Prion diseases)是一类具有致死性、传染性和进行性的神经退行性疾病。研究发现朊病毒感染的细胞和动物模型中均存在着线粒体功能异常和氧化应激,这很有可能在朊病毒病发生发展中起重要作用。为探究线粒体靶向抗氧化剂对朊病毒感染是否具有一定的治疗作用,我们选出两种线粒体靶向抗氧化剂,以一定浓度作用于朊病毒感染神经细胞系,并观察细胞活性和线粒体功能的变化情况。结果显示,Mitoquinone(MitoQ)和积雪草酸(Asiatic acid,AA)这两种药物能够显著提高朊病毒感染细胞的活性,降低其活性氧(Reactive oxygen species,ROS)水平,上调ATP5β的表达水平,提示这两种药物对朊病毒感染细胞有一定的治疗作用,本研究为朊病毒病发病机制以及治疗的研究提供了新的思路。

Mitochondrial dysfunction and oxidative stress are closely linked to the pathogenesis of aging-associated neurodegenerative disorders,including prion diseases.Mitochondria - targeted antioxidants have been proven to be effective in several neurodegenerative diseases.In the present study,we investigated the protective effects of two mitochondria-targeted antioxidants Mitoquinone(MitoQ)and Asiatic Acid(AA)on scrapie infected cell line.Cell viability,intracellular ROS levels,and the expression of ATP5 β and SIRT3 were detected with or without AA treatment.The results showed that the treatment of AA enhanced cell viability.In addition,AA treatment decreased ROS levels,which are elevated in scrapie infected cell line.More interestingly,administration of AA inhibited the decline of ATP5 β.These data indicate that MitoQ and AA could protect scrapie infect- ed cell line and suggest that mitochondria-targeted antioxidants might be developed as agents for prion therapy.