ABSTRACT
The abnormal accumulation of ß-amyloid peptide (Aß) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aß-mediated neurotoxicity remain elusive, Aß 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 Aß-toxicity in transgenic Caenorhabditis elegans overexpressing a human Aß peptide. The accumulation of Aß in this model leads to paralysis and premature death. We show that ET dose-dependently reduces Aß-oligomerization and extends the lifespan and healthspan of the nematodes.
