中山醫學大學機構典藏 CSMUIR:Item 310902500/22345
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    题名: Caffeic acid and resveratrol ameliorate cellular damage in cell and Drosophila models of spinocerebellar ataxia type 3 through upregulation of Nrf2 pathway
    作者: Wu, Yu-Ling;Chang, Jui-Chih;Lin, Wei-Yong;Li, Chien-Chun;Hsieh, Mingli;Chen, Haw-Wen;Wang, Tsu-Shing;Wu, Wen-Tzu;Liu, Chin-San;Liu, Kai-Li
    贡献者: 中山醫學大學;營養系
    关键词: Autophagy;Caffeic acid;Mutant ataxin-3;Nrf2;Oxidative stress;PolyQ diseases;Resveratrol;Spinocerebellar ataxia type 3
    日期: 2018-02-01
    上传时间: 2022-05-17T03:44:57Z (UTC)
    出版者: Elsevier Inc.
    摘要: Polyglutamine (polyQ)-expanded mutant ataxin-3 protein, which is prone to misfolding and aggregation, leads to cerebellar neurotoxicity in spinocerebellar ataxia type 3 (SCA3), an inherited PolyQ neurodegenerative disease. Although the exact mechanism is unknown, the pathogenic effects of mutant ataxin-3 are associated with dysregulation of transcription, protein degradation, mitochondrial function, apoptosis, and antioxidant potency. In the present study we explored the protective role and possible mechanism of caffeic acid (CA) and resveratrol (Res) in cells and Drosophila expressing mutant ataxin-3. Treatment with CA and Res increased the levels of antioxidant and autophagy protein expression with consequently corrected levels of reactive oxygen species, mitochondrial membrane potential, mutant ataxin-3, and the aggregation of mutant ataxin-3 in SK-N-SH-MJD78 cells. Moreover, in SK-N-SH-MJD78 cells, CA and Res enhanced the transcriptional activity of nuclear factor erythroid-derived-2-like 2 (Nrf2), a master transcription factor that upregulates the expression of antioxidant defense genes and the autophagy gene p62. CA and Res improved survival and motor performance in SCA3 Drosophila. Additionally, the above-mentioned protective effects of CA were also observed in CA-supplemented SCA3 Drosophila. Notably, blockade of the Nrf2 pathway by use of small interfering RNA annulled the health effects of CA and Res on SCA3, which affirmed the importance of the increase in Nrf2 activation by CA and Res. Additional studies are need to dissect the protective role of CA and Res in modulating neurodegenerative progression in SCA3 and other polyQ diseases.
    URI: https://ir.csmu.edu.tw:8080/handle/310902500/22345
    關聯: Free Radic Biol Med,115,309-317
    显示于类别:[營養學系暨碩士班] 期刊論文

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