Tyrosol, a simple phenol from EVOO, targets multiple pathogenic mechanisms of neurodegeneration in a C. elegans model of Parkinson´s Disease

Abstract Parkinson's Disease (PD) is a common neurodegenerative disorder involving α-synuclein (α-syn) aggregation, oxidative stress, dysregulation of redox metal homeostasis and neurotoxicity. Different phenolic compounds with known antioxidant or anti-chelating properties have been shown to also interfere with aggregation of amyloid proteins and modulate intracellular signaling pathways. The present study aims to investigate for the first time the effect of tyrosol (TYR), a simple phenol present in Extra Virgin Olive Oil (EVOO), on α-syn aggregation in a C. elegans model of PD and evaluate its potential to prevent α-syn toxicity, neurodegeneration and oxidative stress in this model organism. Our results show that TYR is effective in reducing α-syn inclusions, resulting in a lower toxicity and extended lifespan of treated nematodes. Moreover, TYR delayed α-syn-dependent degeneration of dopaminergic neurons in vivo. TYR treatment also reduced ROS level and promoted the expression of specific chaperones and antioxidant enzymes. Overall, our study puts into perspective TYR potential to be considered as nutraceutical that targets pivotal causal factors in PD.