Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA.
Biomed Res Int. 2018 Jun 10;2018:6726874. doi: 10.1155/2018/6726874. eCollection 2018.
Huntington's disease (HD) is a dominant, late-onset disease characterized by choreiform movements, cognitive decline, and personality disturbance. It is caused by a polyglutamine repeat expansion in the Huntington's disease gene encoding for the Huntingtin protein (Htt) which functions as a scaffold for selective macroautophagy. Mutant Htt (mHtt) disrupts vesicle trafficking and prevents autophagosome fusion with lysosomes, thus deregulating autophagy in neuronal cells, leading to cell death. Autophagy has been described as a therapeutic target for HD, owing to the key role Htt plays in the cellular process. , a plant extract used in traditional medicine in Europe and Asia, has been shown to attenuate aging in the fly and other model species. It has also been shown to inhibit the mTOR pathway and induce autophagy in bladder cancer cell lines. We hypothesized that , by inducing autophagy, may improve the phenotype of a Huntington's disease model of the fly. Flies expressing HttQ93 which exhibit decreased lifespan, impaired locomotion, and increased neurodegeneration were supplemented with extract, and assays testing lifespan, locomotion, and pseudopupil degeneration provided quantitative measures of improvement. Based on our observations, may be further evaluated as a potential therapy for Huntington's disease.
亨廷顿病 (HD) 是一种显性、迟发性疾病，其特征为舞蹈样运动、认知能力下降和人格障碍。它是由亨廷顿病基因编码的亨廷顿蛋白 (Htt) 中的多聚谷氨酰胺重复扩展引起的，该蛋白作为选择性巨自噬的支架。突变型 Htt (mHtt) 破坏囊泡运输并阻止自噬体与溶酶体融合，从而使神经元细胞中的自噬失调，导致细胞死亡。自噬已被描述为 HD 的治疗靶点，这是由于 Htt 在细胞过程中发挥关键作用。, 一种在欧洲和亚洲传统医学中使用的植物提取物，已被证明可以延缓果蝇和其他模式生物的衰老。它还被证明可以抑制 mTOR 通路并诱导膀胱癌细胞系中的自噬。我们假设, 通过诱导自噬，可能会改善果蝇亨廷顿病模型的表型。表达 HttQ93 的果蝇表现出寿命缩短、运动能力受损和神经退行性变增加，用 提取物进行补充，并进行寿命、运动和假瞳孔退化的测定，提供了改善的定量衡量标准。基于我们的观察， 可能会被进一步评估为亨廷顿病的潜在治疗方法。
