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，但对该疾病的基本治疗仍然很少。因此，从药用植物中寻找可用于治疗 PD 的潜在有效化合物引起了人们的极大兴趣。

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形式的硒、N-γ-(L-谷氨酰)-L-硒代甲硫氨酸 (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：我们使用在多巴胺能神经元中特异性表达绿色荧光蛋白 (GFP) 的秀丽隐杆线虫药理学 PD 菌株 (BZ555) 和在肌肉细胞中表达人 α-突触核蛋白 (α-syn) 的转基因 PD 菌株 (NL5901) 进行研究Glu-SeMet 对 PD 的神经保护潜力。

结果：我们发现 Glu-SeMet 显着改善了转基因 BZ555 菌株中 6-羟基多巴胺 (6-OHDA) 诱导的多巴胺能神经元损伤，并相应改善了减缓行为和细胞内 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 诱导的毒性表现出更强的改善作用。Glu-SeMet 还引发了 SKN-1/Nrf2 的核易位，并显着增加了 BZ555 菌株中 SKN-1、GST-4 和 GCS-1 的 mRNA 水平。然而，当 BZ555 菌株受到skn-1 RNA 干扰 (RNAi)时，Glu-SeMet 不会增加 mRNA 水平或改善对多巴胺能神经元的损伤。Glu-SeMet 还上调了 BZ555 和 BZ555 中硒蛋白 TRXR-1 的 mRNA 水平；skn-1 RNAi 菌株并显着降低 NL5901 菌株中 α-syn 的积累，尽管这在 NL5901 中未观察到；trxr-1菌株。

结论：我们发现 Glu-SeMet在线虫PD 模型中对 PD 具有神经保护作用，并且 Glu-SeMet的抗 PD 作用与 SKN-1/Nrf2 和 TRXR-1 相关。因此，Glu-SeMet 有可能用于治疗应用或补充剂以减缓 PD 的进展。