Inhibition of amyloid-induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model

The abnormal accumulation of beta-amyloid peptide (A beta) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of A beta-mediated neurotoxicity remain elusive, A beta has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione-derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET's potential to counteract A beta-toxicity in transgenic Caenorhabditis elegans overexpressing a human A beta peptide. The accumulation of A beta in this model leads to paralysis and premature death. We show that ET dose-dependently reduces A beta-oligomerization and extends the lifespan and healthspan of the nematodes.