Publication date: Sep 03, 2019
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 is insufficient for HD disease, 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 Caenorhabditis elegans (C. elegans). At low dosages, Nano-Se NPs significantly reduced neuronal death, relieved behavioral dysfunction, and protected C. elegans from damages in stress conditions. Molecular mechanism also revealed that Nano-Se attenuated oxidative stress, inhibited the aggregation of huntingtin proteins, and down regulated 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, mechanism about how Nano-Se NPs protect from damages in stress conditions and repair neural functions will benefit to 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.
Cong, W., Bai, R., Li, Y.F., Wang, L., and Chen, C. Selenium Nanoparticles as an Efficient Nanomedicine for the Therapy of Huntington’s Disease. 06665. 2019 ACS Appl Mater Interfaces.
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