秀丽隐杆线虫
自噬
神经保护
神经退行性变
基因敲除
RNA干扰
生物
细胞生物学
未折叠蛋白反应
线粒体
化学
分子生物学
基因
药理学
生物化学
细胞凋亡
核糖核酸
疾病
医学
内质网
病理
作者
Minglv Fang,Ying Liu,Xiaoyan Gao,Jing Yu,Xiaohui Tu,Xueying Mo,Huanhu Zhu,Yan Zou,Cheng Huang,Shengjie Fan
摘要
Abstract Huntington's disease (HD) is a fatal neurodegenerative disease associated with autophagy disorder and mitochondrial dysfunction. Here, we identified therapeutic potential of perillaldehyde (PAE), a monoterpene compound obtained from Perilla frutescens (L.) Britt., in the Caenorhabditis elegans ( C. elegans ) model of HD, which included lifespan extension, healthspan improvement, decrease in polyglutamine (polyQ) aggregation, and preservation of mitochondrial network. Further analyses indicated that PAE was able to induce autophagy and mitochondrial unfolded protein reaction (UPR mt ) activation and positively regulated expression of associated genes. In lgg‐1 RNAi C. elegans or C. elegans with UPR mt ‐related genes knockdown, the effects of PAE treatment on polyQ aggregation or rescue polyQ‐induced toxicity were attenuated, suggesting that its neuroprotective activity depended on autophagy and UPR mt . Moreover, we found that pharmacological and genetic activation of UPR mt generally protected C. elegans from polyQ‐induced cytotoxicity. Finally, PAE promoted serotonin synthesis by upregulating expression of TPH‐1, and serotonin synthesis and neurosecretion were required for PAE‐mediated UPR mt activation and its neuroprotective activity. In conclusion, PAE is a potential therapy for polyQ‐related diseases including HD, which is dependent on autophagy and cell‐non‐autonomous UPR mt activation.
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