Ergothioneine exerts neuroprotective effects in Parkinson's disease: Targeting α-synuclein aggregation and oxidative stress.

Ergothioneine (EGT) is a natural dietary antioxidant derived from certain edible mushrooms, commonly used as a food additive and supplement, but its effects on Parkinson's Disease (PD) are still unclear. The accumulation of α-synuclein (α-syn) plays a pivotal role in the pathogenesis and development of PD. Here, this study demonstrated that EGT effectively inhibits α-syn aggregation, disrupts mature fibers, and reduces associated cytotoxicity and oxidative stress. The beneficial effects of EGT were confirmed in Caenorhabditis elegans, where it protected dopaminergic neurons, prolonged lifespan and enhanced behavioral functions by reducing α-syn plaque accumulation and associated oxidative stress. Molecular dynamics simulation revealed that EGT interacts directly with α-syn pentamer through van der Waals and electrostatic forces, disrupting the structural stability of the preformed pentamer. Furthermore, animal studies validated that EGT alleviated neuronal damage and improved behavioral deficits by reducing α-syn aggregation, oxidative stress and inflammatory response. In conclusion, EGT presents promising potential as a dietary supplement for preventing and alleviating PD.