Geraniol Protects Against Oxidative Stress And Proteotoxicity In C. Elegans Parkinson’s Disease Models

Abstract

The rise in life expectancy has led to an increase in age-related disorders, including neurodegenerative diseases (ND). Oxidative stress (OS) plays a crucial role in the progression of these conditions. For instance, in Parkinson’s disease (PD), impaired free radical scavenging results in α-synuclein (α-syn) aggregation and subsequent proteotoxic damage. Geraniol (GER), a plant-derived essential oil, is well-known for its potent antioxidant properties. Given the association between OS and ND, antioxidant compounds are attractive as potential therapeutic agents. In this study, we investigated the effects of GER in C. elegans models of PD, where α-syn is expressed either in muscle or dopaminergic neurons. Our findings show that GER treatment improves locomotion, reduces α-syn accumulation, and protects dopaminergic neurons from degeneration. Thus, these results demonstrate GER’s protective effect against proteotoxicity caused by α-syn aggregation. Additionally, GER enhances OS resistance in C. elegans. To further explore GER’s protective mechanisms, we analyzed null mutants in key OS-related pathways. Our results indicate that the transcription factors SKN1/NRF2 and HSF1 play crucial roles in mediating GER’s antioxidant effects. Preliminary data also suggest that GER may modulate autophagy, contributing to its neuroprotective actions. In conclusion, this work demonstrates the potential anti neurodegenerative effects of GER in vivo, which should be validated in other models