Rutin protects Huntington's disease through the insulin/IGF1 (IIS) signaling pathway and autophagy activity: Study in Caenorhabditis elegans model

Abstract

Huntington's disease (HD) is inherited neurodegenerative disease, it is characterized by excessive motor movements and cognitive and emotional deficits. HD is caused by an abnormally long polyglutamine (polyQ) expansion in the huntingtin (Htt) protein, 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 previous studies have already indicated that rutin has some protective effects in HD's models, the underlying mechanisms are still unknown. In our study, we investigated the effects of rutin in Caenorhabditis elegans model of HD. We assessed polyQ aggregation, oxidative damage, neurodegeneration level and lifespan, and investigated the possible role of autophagy and insulin/IGF1 (IIS) signaling pathways in the beneficial effects induced by rutin. Overall, our data demonstrate that chronic rutin treatment reduced polyglutamine (polyQ) protein aggregation in muscle, reduced polyQ-mediated neuronal death in ASH sensory neurons, and extended lifespan. The possible mechanisms involved are antioxidant activity, activation of protein degradation (autophagy) and insulin/IGF1 (IIS) signaling pathways. These findings indicate that rutin consumption might be helpful in preventing HD and also provide possible pathways to be explored to search for new therapies against proteinopathies related to aging.

Keywords: C. elegans; Flavonoids; Neurodegeration; Proteinopathies.