Franzen da Silva, Aline, Valandro Soares, Marcell, Antunes Soares, Felix, Arantes, Leticia, Obetine, Fabiane, Lopes Machado, Marina, da Silveira, Tassia, Marafiga Cordeiro, Larissa
[
International Worm Meeting,
2021]
Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disease. It occurs due to a mutation in the huntingtin gene with an abnormal CAG repeat, leading to a variable length N-terminal polyglutamine chain (poly-Q) which confers toxic functions to mutant Htt leading to neurodegeneration. Rutin is a flavonoid found in plants, buckwheat, some teas and also in apples. Although our previous studies have already indicated that rutin has protective effects in HD's models, more studies are needed to unravel its effects on protein homeostasis and the underlying mechanisms. In our study, we investigated the effects of chronic treatment with rutin in Caenorhabditis elegans model of HD focusing on ASH neurons and antioxidant defense. The synchronized L1 worms were placed on rutin-NGM plates and kept at 20°C. Rutin was added every 24 hours at concentrations of 15, 30, 60 and 120 muM. We assessed octanol response, neuronal polyQ aggregates and dye filling assay. In addition, we analyzed the downstream heat-shock protein-16.2 (HSP-16.2) and superoxide dismutase-3 (SOD-3). Overall, our data demonstrate that chronic rutin treatment maintains the function of ASH neurons in addition to decrease the degeneration of their sensory terminations. The mechanism proposed is antioxidant activity, through the overexpression of antioxidant enzymes and chaperones regulating proteostasis. Our findings provide new evidences about rutin playing a neuroprotective role in C elegans model. In addition to information for treatment strategies for neurodegenerative diseases and other diseases caused by age-related protein aggregation.