Title : Using C. elegans as a Model System to Identify Antioxidant Therapeutics for Neurodegenerative Diseases

The increase in life expectancy has led to a growing prevalence of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases. A key contributor to their progression is oxidative stress, which promotes protein aggregation and proteotoxic damage. This makes antioxidant compounds attractive candidates for therapeutic intervention.

In this work, we used Caenorhabditis elegans models of neurodegeneration to evaluate the in vivo antioxidant and neuroprotective effects of synthetic and natural compounds. By combining genetic, pharmacological, microscopy, and behavioral approaches, we investigated both functional outcomes and underlying molecular mechanisms.

We identified the synthetic imidazole derivative 1-mesityl-3-(3-sulfonatopropyl)imidazolium (MSI) and the natural compound geraniol as enhancers of oxidative stress resistance. Importantly, both compounds significantly delayed the onset of proteotoxic phenotypes in C. elegans models of Alzheimer’s, Parkinson’s, and Huntington’s diseases, reducing protein aggregation and neurodegeneration.

Mechanistically, we found that MSI requires the transcription factor HSF-1 to exert its protective effects. In contrast, the activity of geraniol depends on SKN-1/Nrf2 and DAF-16/FOXO pathways. Additionally, microscopy analyses suggest that geraniol may promote autophagy, further contributing to its neuroprotective properties.

Overall, our findings demonstrate that antioxidant compounds can confer robust protection against proteotoxicity in vivo and highlight C. elegans as a powerful platform for the identification of potential therapeutics for neurodegenerative diseases.

Dr. De Rosa has led the Invertebrate Neurobiology Laboratory at the Institute of Biochemical Research of Bahía Blanca, Argentina, since 2014, where she also earned her PhD. She completed a postdoctoral fellowship at the University of Massachusetts, USA.

She is currently a researcher at CONICET and a professor at the University of the South. Dr. De Rosa has authored more than 20 publications in prestigious international journals. Her research focuses on neurobiology and neuropharmacology, particularly the molecular mechanisms underlying these processes, using the invertebrate Caenorhabditis elegans as a model organism