Ergothioneine Prevents Neuronal Cell Death Caused by the Neurotoxin 6-Hydroxydopamine

Abstract

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.

Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons

“…VHCL inhibited the protective effect of ET on mitochondrial dysfunction. Our results add to previous findings that ET has neuroprotective functions [ 21 , 26 , 28 , 43 ] which could potentially aid in the prevention and treatment of PD. We would also like to acknowledge the paper that was published by Yuzawa et al (2024) [ 43 ] while we were preparing this manuscript.…”

“…Our results add to previous findings that ET has neuroprotective functions [ 21 , 26 , 28 , 43 ] which could potentially aid in the prevention and treatment of PD. We would also like to acknowledge the paper that was published by Yuzawa et al (2024) [ 43 ] while we were preparing this manuscript. Yuzawa et al reported the protective effect of ET against 6-OHDA neurotoxin in immortalised mouse hypothalamic cells (GT-17), a cell line perhaps less relevant to PD.…”

“…Discovery of potential mitochondrial protectants that could cross the BBB could be highly valuable, given the role of mitochondrial dysfunction in PD [ 11 , 12 , 13 , 14 , 15 , 41 , 42 ]. Yuzawa et al (2024) [ 43 ] reported the protective effect of ET against 6-OHDA neurotoxicity in immortalised mouse hypothalamic cells (GT-17) through reduction in endoplasmic reticulum stress response. Thus far, however, it is not known if ET could protect against damage using cell models more relevant to human PD, such as human induced pluripotent stem cell (hiPSC)-derived dopaminergic neurons.…”