N-γ-(L-谷氨酰基)-L-硒代蛋氨酸对秀丽隐杆线虫 SKN-1/Nrf2 和 TRXR-1 相关帕金森病具有神经保护作用。
N-γ-(L-glutamyl)-L-selenomethionine shows neuroprotective effects against Parkinson's disease associated with SKN-1/Nrf2 and TRXR-1 in Caenorhabditis elegans.
机构信息
Department of Bioenvironmental Systems Engineering, National Taiwan University, No. 1 Roosevelt Road, Sec. 4, Taipei 106, Taiwan.
Institute of Food Safety and Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei 100, Taiwan; Department of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei, 100, Taiwan.
出版信息
Phytomedicine. 2021 Nov;92:153733. doi: 10.1016/j.phymed.2021.153733. Epub 2021 Sep 4.
BACKGROUND
Parkinson's disease (PD) is a common neurodegenerative disease, yet fundamental treatments for the disease remain sparse. Thus, the search for potentially efficacious compounds from medicinal plants that can be used in the treatment of PD has gained significant interest.
PURPOSE
In many medicinal plants, selenium is primarily found in an organic form. We investigated the neuroprotective potential of an organic form of selenium, N-γ-(L-glutamyl)-L-selenomethionine (Glu-SeMet) in a Caenorhabditis elegans PD model and its possible molecular mechanisms.
METHODS
We used a C. elegans pharmacological PD strain (BZ555) that specifically expresses green fluorescent protein (GFP) in dopaminergic neurons and a transgenic PD strain (NL5901) that expresses human α-synuclein (α-syn) in muscle cells to investigate the neuroprotective potential of Glu-SeMet against PD.
RESULTS
We found that Glu-SeMet significantly ameliorated 6-hydroxydopamine (6-OHDA)-induced dopaminergic neuron damage in the transgenic BZ555 strain, with corresponding improvements in slowing behavior and intracellular ROS levels. In addition, compared with clinical PD drugs (L-DOPA and selegiline), Glu-SeMet demonstrated stronger ameliorated effects on 6-OHDA-induced toxicity. Glu-SeMet also triggered the nuclear translocation of SKN-1/Nrf2 and significantly increased SKN-1, GST-4, and GCS-1 mRNA levels in the BZ555 strain. However, Glu-SeMet did not increase mRNA levels or ameliorate the damage to dopaminergic neurons when the BZ555 strain was subjected to skn-1 RNA interference (RNAi). Glu-SeMet also upregulated the mRNA levels of the selenoprotein TRXR-1 in both the BZ555 and BZ555; skn-1 RNAi strains and significantly decreased α-syn accumulation in the NL5901 strain, although this was not observed in the NL5901; trxr-1 strain.
CONCLUSION
We found that Glu-SeMet has a neuroprotective effect against PD in a C. elegans PD model and that the anti-PD effects of Glu-SeMet were associated with SKN-1/Nrf2 and TRXR-1. Glu-SeMet may thus have the potential for use in therapeutic applications or supplements to slow the progression of PD.
背景
帕金森病（PD）是一种常见的神经退行性疾病，但基本的治疗方法仍然很少。因此，从药用植物中寻找可能有效的化合物来治疗 PD 引起了极大的关注。
目的
在许多药用植物中，硒主要以有机形式存在。我们研究了一种有机硒形式 N-γ-（L-谷氨酰基）-L-硒代蛋氨酸（Glu-SeMet）在秀丽隐杆线虫 PD 模型中的神经保护潜力及其可能的分子机制。
方法
我们使用了一种专门在多巴胺能神经元中表达绿色荧光蛋白（GFP）的秀丽隐杆线虫药理学 PD 菌株（BZ555）和一种在肌肉细胞中表达人类α-突触核蛋白（α-syn）的转基因 PD 菌株（NL5901）来研究 Glu-SeMet 对 PD 的神经保护潜力。
结果
我们发现 Glu-SeMet 显著改善了 6-羟多巴胺（6-OHDA）诱导的 BZ555 转基因菌株多巴胺能神经元损伤，同时改善了运动迟缓行为和细胞内 ROS 水平。此外，与临床 PD 药物（L-DOPA 和司来吉兰）相比，Glu-SeMet 对 6-OHDA 诱导的毒性具有更强的改善作用。Glu-SeMet 还触发了 SKN-1/Nrf2 的核转位，并显著增加了 BZ555 菌株中 SKN-1、GST-4 和 GCS-1 mRNA 的水平。然而，当 BZ555 菌株进行 skn-1 RNAi 时，Glu-SeMet 并没有增加 mRNA 水平或改善多巴胺能神经元的损伤。Glu-SeMet 还上调了 BZ555 和 BZ555;skn-1 RNAi 菌株中 selenoprotein TRXR-1 的 mRNA 水平，并显著降低了 NL5901 菌株中 α-syn 的积累，但在 NL5901;trxr-1 菌株中没有观察到这种情况。
结论
我们发现 Glu-SeMet 对秀丽隐杆线虫 PD 模型具有神经保护作用，Glu-SeMet 的抗 PD 作用与 SKN-1/Nrf2 和 TRXR-1 有关。因此，Glu-SeMet 可能具有用于治疗应用或补充剂的潜力，以减缓 PD 的进展。
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