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木犀草素作为亨廷顿病治疗的潜在药物:来自转基因小鼠模型的见解。

Luteolin as potential treatment for Huntington's disease: Insights from a transgenic mouse model.

机构信息

Department of Basic Medical Sciences, College of Medicine-Dar Al Uloom University, Riyadh, Saudi Arabia.

Department of Histology and Embryology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

CNS Neurosci Ther. 2024 Sep;30(9):e70025. doi: 10.1111/cns.70025.

Abstract

AIMS

The study aimed to evaluate the potential benefits of luteolin treatment in Huntington's disease (HD), an inherited progressive neurodegenerative disorder.

METHODS

HD N171-82Q transgenic and WT mice received luteolin or vehicle for treatment at 6 weeks of age. The mice's body weight changes and survival rates were monitored throughout the study, and a series of motor functional tests were conducted. Serum level of the marker NfL was also determined. Immunohistochemical staining and western blotting were utilized to assess the expression of huntingtin aggregates.

RESULTS

Luteolin treatment enhanced survival and prevented weight loss in HD mice compared to the vehicle-treated HD group. Furthermore, the luteolin-treated HD mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction. Also, luteolin decreased serum NfL levels in HD mice. Notably, the accumulation of huntingtin aggregates was significantly reduced in the brain's cortex, hippocampus, and striatum of luteolin-treated HD mice compared to the vehicle-treated HD group.

CONCLUSION

Luteolin holds promise as a therapeutic agent for improving survival outcomes, managing motor dysfunction, and reducing huntingtin aggregates in HD. The findings are of significance as currently, there are no approved therapeutic interventions that reverse HD pathology or slow down its progression.

摘要

目的

本研究旨在评估木樨草素治疗亨廷顿病(HD)的潜在益处,HD 是一种遗传性进行性神经退行性疾病。

方法

HD N171-82Q 转基因和 WT 小鼠在 6 周龄时接受木樨草素或载体治疗。在整个研究过程中监测小鼠的体重变化和存活率,并进行一系列运动功能测试。还测定了血清标志物 NfL 的水平。免疫组织化学染色和 Western blot 用于评估亨廷顿蛋白聚集物的表达。

结果

与载体处理的 HD 组相比,木樨草素治疗可提高 HD 小鼠的存活率并预防体重减轻。此外,木樨草素处理的 HD 小鼠表现出增强的运动协调和平衡能力,显著减少运动功能障碍。此外,木樨草素降低了 HD 小鼠的血清 NfL 水平。值得注意的是,与载体处理的 HD 组相比,木樨草素处理的 HD 小鼠大脑皮质、海马体和纹状体中的亨廷顿蛋白聚集物明显减少。

结论

木樨草素有望成为改善 HD 患者生存结局、管理运动功能障碍和减少亨廷顿蛋白聚集物的治疗药物。鉴于目前尚无逆转 HD 病理或减缓其进展的批准治疗干预措施,这一发现意义重大。

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