CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology of China , Beijing 100190 , China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics , Chinese Academy of Sciences , Beijing 100049 , China.
ACS Appl Mater Interfaces. 2019 Sep 25;11(38):34725-34735. doi: 10.1021/acsami.9b12319. Epub 2019 Sep 12.
Huntington's disease (HD) is an incurable disease with progressive loss of neural function, which is influenced by epigenetic, oxidative stress, metabolic, and nutritional factors. Targeting inhibition of huntingtin protein aggregation is a strategy for HD therapy, but the efficacy is unsatisfactory. Studies found that selenium (Se) levels in the brain are insufficient for HD disease individuals, while improvement in Se homeostasis in the brain may attenuate neuronal loss and dysfunction. In this study, we applied selenium nanoparticles (NPs) (Nano-Se) for the HD disease therapy by regulating HD-related neurodegeneration and cognitive decline based on transgenic HD models of (). At low dosages, Nano-Se NPs significantly reduced neuronal death, relieved behavioral dysfunction, and protected from damages in stress conditions. The molecular mechanism further revealed that Nano-Se attenuated oxidative stress, inhibited the aggregation of huntingtin proteins, and downregulated the expression of histone deacetylase family members at mRNA levels. The results suggested that Nano-Se has great potential for Huntington's disease therapy. In conclusion, the mechanism about how Nano-Se NPs protect from damages in stress conditions and how they repair neural functions will benefit HD disease therapy. This study will also guide rational design of Nano-Se NPs or other selenium compounds to improve HD therapy in the future.
亨廷顿病（HD）是一种不可治愈的神经功能进行性丧失疾病，受表观遗传、氧化应激、代谢和营养因素的影响。针对亨廷顿蛋白聚集的抑制是 HD 治疗的一种策略，但疗效并不理想。研究发现，HD 患者大脑中的硒（Se）水平不足，而改善大脑中的 Se 动态平衡可能减轻神经元丢失和功能障碍。在这项研究中，我们应用硒纳米颗粒（NPs）（Nano-Se）通过调节与转基因 HD 模型相关的神经退行性变和认知下降来治疗 HD 疾病（）。在低剂量下，Nano-Se NPs 显著减少神经元死亡，缓解行为功能障碍，并在应激条件下保护免受损伤。分子机制进一步表明，Nano-Se 减轻氧化应激，抑制亨廷顿蛋白的聚集，并在 mRNA 水平下调组蛋白去乙酰化酶家族成员的表达。结果表明，Nano-Se 具有治疗亨廷顿病的巨大潜力。总之，Nano-Se NPs 如何保护免受应激条件下的损伤以及如何修复神经功能的机制将有益于 HD 疾病的治疗。这项研究也将指导未来合理设计 Nano-Se NPs 或其他硒化合物以改善 HD 治疗。
