Geraniol protects against oxidative stress and proteotoxicity in Caenorhabditis elegans Parkinson's disease models

Abstract

Due to the increase in life expectancy worldwide, age-related disorders such as neurodegenerative diseases have become more prevalent. Elevated levels of oxidative stress could modulate the progression of neurodegenerative diseases. For example, in Parkinson’s disease it has been shown that compromising the capacity to scavenge free radicals can exacerbate α-synuclein (α-syn) aggregation and proteotoxic damage. Geraniol, a plant-derived essential oil, has recognized antioxidant properties. Considering that oxidative stress contributes to proteotoxic disease progression, compounds with antioxidant activity have been postulated as potential therapeutic agents. C.elegans is widely used in biomedical research. There is a high level of homology between C. elegans and mammalian genes (including proteins involved in cytoprotective mechanisms). In fact, several neurodegenerative diseases can be recapitulated in this animal. In this work, we use C. elegans Parkinson’s disease models to evaluate the in vivo effect of geraniol. We found that geraniol improves impaired locomotion in these animal models. Interestingly, geraniol also decreases α-syn aggregation. In addition, our last preliminary results suggest that DAF-16 is not involved in geraniol activity. So far, these results indicate a potential antiproteotoxic effect of this drug in C. elegans Parkinson’s disease models. Therefore, we propose to combine genetic, microscopy and behavioral techniques to unravel geraniol effect in C. elegans neurodegenerative diseases models. These studies could provide a proof of concept of the potential of geraniol as a promising compound to retard proteotoxic diseases.