Potential Protection Against Parkinson’s Disease by Ergothioneine—Nature’s Multifactorial Neuroprotectant

The use of neuroprotective nutraceuticals as a strategy against neurodegenerative diseases such as Parkinson’s disease (PD) has gained considerable traction in recent years. In this review, we highlight ergothioneine (ET)—a naturally occurring thiol/thione derivative abundant in mushrooms—as a promising candidate, given its long half-life, blood–brain barrier penetration, and high bioavailability. Numerous population studies have linked low blood ET levels with increased risk and progression of neurological and other age-related disorders in humans, suggesting that dietary ET may confer neuroprotective benefits. Supporting this, several studies have demonstrated the efficacy of ET treatment in reducing PD-associated molecular damage across various pre-clinical models such as C. elegans, Drosophila, rodent models and human neuronal cultures, leading to marked improvements in disease phenotypes. Here, we summarize some of the proposed mechanisms by which ET may exert neuroprotection in PD, including the reduction of protein aggregation, enhancement of mitochondrial function, mitigation of oxidative stress, and attenuation of apoptosis and neuroinflammation. We also highlight recent clinical trials demonstrating the safety and potential efficacy of ET and propose future research to facilitate the translation of ET into the clinic.