L-Ergothioneine ameliorates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease in C57BL/6J mice by activating DJ-1  

作　　者：Xianshe Meng Huawen Meng Shuzeng Hou Zequn Yin Xuerui Wang Ke Gong Feng Zhang Qingshan Li Shuang Zhang Yuanli Chen Xiaoxiao Yang Zhiwei Zhao Chenzhong Liao Yajun Duan 

机构地区：[1]Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes,College of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,China [2]Department of Cardiology,The First Affi liated Hospital of University of Science and Technology of China,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China

出　　处：《Food Science and Human Wellness》2025年第3期1045-1061,共17页食品科学与人类健康(英文)

基　　金：supported by the National Natural Science Foundation of China(U22A20272,82173807,82170497)。

摘　　要：Parkinson's disease(PD)is one of the most common neurodegenerative diseases.The loss of dopaminergic(DAergic)neurons in the substantia nigra and the decrease of dopamine(DA)levels accelerate the process of PD.L-Ergothioneine(EGT)is a natural antioxidant derived from microorganisms,especially in edible mushrooms.EGT can penetrate blood-brain barrier and its levels are significantly decreased in the plasma of PD patients.Therefore,we speculated that EGT could ameliorate PD,and determined its effect on PD development by using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse models and neurotoxin 1-methyl-4-phenylpyridinium(MPP^(+))-induced cell models.Our results show that EGT alleviated MPTP-induced behavioral dysfunction in mice.Mechanistically,we innovatively revealed that EGT was a key regulator of DJ-1.EGT restored DA levels by activating the DJ-1-nuclear receptor-related factor 1(Nurr1)axis.Furthermore,it reduced reactive oxygen species(ROS)levels by regulating the DJ-1-nuclear factor erythroid 2-related factor 2(Nrf2)pathway,which inhibited oxidative stress-induced DAergic neuronal apoptosis.Combined treatment with DJ-1-si RNA transfection revealed that blocking DJ-1 reversed EGT upregulated Nurr1 and Nrf2 expression in the nucleus,which significantly decreased the benefits of EGT.Taken together,our study suggests that EGT can ameliorate PD and be considered as a strategy for PD treatment.

关 键 词：L-Ergothioneine 1-Methyl-4-phenyl-1 2 3 6-TETRAHYDROPYRIDINE Parkinson’s disease DJ-1 Dopaminergic neurons 

分 类 号：R74[医药卫生—神经病学与精神病学]