Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo, Tokyo 202-8585, Japan.
Euglena, Co., Ltd., 5-29-11 G-BASE Tamachi 2nd Floor Shiba, Minato-ku, Tokyo 108-0014, Japan.
Cells. 2024 Jan 25;13(3):230. doi: 10.3390/cells13030230.
Neuronal cell death is a key mechanism involved in the development and exacerbation of Parkinson's disease (PD). The excessive production of reactive oxygen species (ROS) is a major cause leading to neuronal death; therefore, compounds that prevent oxidative stress-dependent neuronal death may be promising as a preventive method for PD. Ergothioneine is a natural amino acid with antioxidant properties, and its protective functions in the body are attracting attention. However, there has been no investigation into the protective functions of ergothioneine using in vivo and in vitro PD models. Thus, in this study, we analyzed the efficacy of ergothioneine against 6-hydroxydopamine (6-OHDA)-dependent neuronal cell death using immortalized hypothalamic neurons (GT1-7 cells). First, we found that ergothioneine prevents 6-OHDA-dependent neuronal cell death by suppressing ROS overproduction in GT1-7 cells. The cytoprotective effect of ergothioneine was partially abolished by verapamil, an inhibitor of OCTN1, which is involved in ergothioneine uptake. Furthermore, ergothioneine-rich Rice-koji (Ergo-koji) showed cytoprotective and antioxidant effects similar to those of ergothioneine. Taken together, these results suggest that ergothioneine or foods containing ergothioneine may be an effective method for preventing the development and progression of PD.
神经元细胞死亡是帕金森病(PD)发展和恶化的关键机制。活性氧(ROS)的过度产生是导致神经元死亡的主要原因;因此,预防氧化应激依赖性神经元死亡的化合物可能是预防 PD 的一种有前途的方法。麦角硫因是一种具有抗氧化特性的天然氨基酸,其在体内的保护功能正引起关注。然而,目前还没有使用体内和体外 PD 模型来研究麦角硫因的保护功能。因此,在这项研究中,我们使用永生下丘脑神经元(GT1-7 细胞)分析了麦角硫因对 6-羟多巴胺(6-OHDA)依赖性神经元细胞死亡的疗效。首先,我们发现麦角硫因通过抑制 GT1-7 细胞中 ROS 的过度产生来预防 6-OHDA 依赖性神经元细胞死亡。OCTN1 抑制剂维拉帕米部分消除了麦角硫因的细胞保护作用,OCTN1 参与麦角硫因的摄取。此外,富含麦角硫因的米曲(Ergo-koji)表现出与麦角硫因相似的细胞保护和抗氧化作用。综上所述,这些结果表明,麦角硫因或含有麦角硫因的食物可能是预防 PD 发展和进展的有效方法。