Protective roles of imidazolium salts in C. elegans models of stress and neurodegeneration

FARIÑA, M.; DE ROSA, M.J.; VEUTHEY, T.; RAYES, D.H.; ANDERSEN, N.; SILBESTRI, G.F

Rosario, Santa Fe

Congreso; Second Latin American Worm Meeting; 2020

In this study, we aim to evaluate the role of imidazolium salts as antioxidant and anti-aging agents.We synthesized imidazolium salts and use the nematode C. elegans to performed a screening toanalyze their ability to improve oxidative stress (OS) resistance. We identified a derivate, 1-Mesithyl-3-(3-sulfonatopropyl)imidazolium (MSI), that enhances animal resistance to OS. Todelineate MSI roles, we split this work into two goals: i) to evaluate MSI role in neurodegenerativemodels, and, ii) to describe the mechanism of action underlying its protective effects.There is a theory that links OS to aging and neurodegeneration. To evaluate MSI neuroprotection,we used C. elegans models of neurodegenerative diseases. As an Alzheimer disease (AD) model,we used a strain that expresses Aβ1-42 in muscle and shows age-dependent protein aggregationand paralysis. Our results show that MSI delays paralysis in this strain. Since mean lifespan ispreserved in wild-type worms exposed to MSI, anti-aging effects of MSI in AD model seems to bedependent on its antiproteotoxic role. To gain further insight into its role in other neurotoxicmodels, we evaluate mobility as an indicator of healthspan in Huntington disease (HD) andParkinson disease (PD) models. We found that MSI ameliorates mobility rate decline in theseproteotoxic models of neurodegenerative diseases.As a first approach to delineate its mechanism of action, we evaluated MSI ability to activate DAF-16 (FOXO in vertebrates), a transcription factor relevant for cytoprotective defense mechanisms.We found that MSI stress protection was not dependent on DAF-16. Therefore, other transcriptionfactors (such as SKN-1 (Nrf-2 in vertebrates), HSF-1), could be involved in MSI protection.Additional research is needed to underpin the mechanism responsible for MSI?s protective roleand to confirm if these effects can be extrapolated to other neurodegenerative scenarios.