State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Food Funct. 2020 Feb 26;11(2):1334-1348. doi: 10.1039/c9fo02131k.
Huntington's disease (HD) is a genetic neurodegenerative disorder caused by a highly polymorphic CAG trinucleotide repeat expansion encoding an extended polyglutamine (polyQ) tract at the N-terminus of huntingtin protein (HTT). The polyQ tract promotes the formation of toxic oligomers and aggregates of HTT, which leads to neuronal dysfunction and death. Therapies to lower mutant HTT (mHTT) and its aggregates appear to be the most promising strategies. Ellagic acid (EA) has been marketed as a dietary supplement with various claimed benefits and neuroprotective effects on several neurodegenerative disorders, while its effect on mHTT pathology is still unknown. Here we reported that EA significantly attenuated motor and cognitive deficits in R6/2 mice. Moreover, EA significantly lowered mHTT levels, reduced neuroinflammation, rescued synapse loss, and decreased oxidative stress in R6/2 mouse brains. These findings indicated that EA has promising therapeutic potential for HD treatment.
亨廷顿病（HD）是一种由高度多态性 CAG 三核苷酸重复扩展引起的遗传性神经退行性疾病，该重复扩展编码在 huntingtin 蛋白（HTT）的 N 端的延伸多聚谷氨酰胺（polyQ）片段。polyQ 片段促进了 HTT 的毒性寡聚体和聚集体的形成，导致神经元功能障碍和死亡。降低突变 HTT（mHTT）及其聚集体的疗法似乎是最有前途的策略。鞣花酸（EA）已作为膳食补充剂销售，具有多种声称的益处，并对几种神经退行性疾病具有神经保护作用，但其对 mHTT 病理学的影响尚不清楚。在这里，我们报道 EA 可显著减轻 R6/2 小鼠的运动和认知缺陷。此外，EA 还可显著降低 mHTT 水平，减轻神经炎症，挽救 R6/2 小鼠大脑中的突触损失，并降低氧化应激。这些发现表明 EA 具有治疗 HD 的潜在治疗潜力。
