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α-Arbutin Protects Against Parkinson's Disease-Associated Mitochondrial Dysfunction In Vitro and In Vivo.
NeuroMolecular Medicine ( IF 3.5 ) Pub Date : 2019-08-10 , DOI: 10.1007/s12017-019-08562-6
Yaqi Ding 1 , Deqin Kong 2 , Tong Zhou 1 , Nai-di Yang 1 , Chenqi Xin 1 , Jiajia Xu 1 , Qi Wang 1 , Hang Zhang 1 , Qiong Wu 1 , Xiaomei Lu 1 , Kahleong Lim 3 , Bo Ma 4 , Chengwu Zhang 1 , Lin Li 1 , Wei Huang 1, 5
Affiliation  

Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of dopaminergic neurons in substantia nigra. The underlying mechanisms of PD pathogenesis have not been fully illustrated and currently PD remains incurable. Accumulating evidences suggest that mitochondrial dysfunction plays pivotal role in the dopaminergic neuronal death. Therefore, discovery of novel and safe agent for rescuing mitochondrial dysfunction would benefit PD treatment. Here we demonstrated for the first time that α-Arbutin (Arb), a natural polyphenol extracted from Ericaceae species, displayed significant protective effect on the rotenone (Rot)-induced mitochondrial dysfunction and apoptosis of human neuroblastoma cell (SH-SY5Y). We further found that the neuroprotective effect of Arb was associated with ameliorating oxidative stress, stabilizing of mitochondrial membrane potential, and enhancing adenosine triphosphate production. To investigate the underlying mechanism, we checked the AMP-activated protein kinase and autophagy pathway and we found that both were involved in the neuroprotection of Arb. Moreover, we explored the protective effect of Arb in drosophila PD model and found that Arb rescued parkin deficiency-induced motor function disability and mitochondrial abnormality of drosophila. Taken together, our study demonstrated that Arb got excellent neuroprotective effect on PD models both in vitro and in vivo and Arb might serve as a potent therapeutic agent for the treatment of PD.

中文翻译:

α-熊果苷在体内和体内可预防帕金森氏病相关的线粒体功能障碍。

帕金森氏病(PD)是最常见的神经退行性运动障碍,其特征是黑质中多巴胺能神经元的进行性丧失。PD发病机理的潜在机制尚未完全阐明,目前PD仍无法治愈。越来越多的证据表明,线粒体功能障碍在多巴胺能神经元死亡中起关键作用。因此,发现一种新颖,安全的线粒体功能障碍治疗药物将有利于PD治疗。在这里,我们首次证明了从毛ric科中提取的天然多酚α-熊果苷(Arb)物种对鱼藤酮(Rot)诱导的线粒体功能障碍和人类神经母细胞瘤细胞(SH-SY5Y)的凋亡具有显着的保护作用。我们进一步发现Arb的神经保护作用与减轻氧化应激,稳定线粒体膜电位和增强三磷酸腺苷的产生有关。为了研究其潜在机制,我们检查了AMP激活的蛋白激酶和自噬途径,发现两者均与Arb的神经保护有关。此外,我们探讨了Arb在果蝇PD模型中的保护作用,并发现Arb挽救了帕金缺乏引起的运动功能障碍和果蝇的线粒体异常。在一起
更新日期:2019-08-10
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