Dietary supplementation with peptides from sesame cake protect Caenorhabditis elegans from polyglutamine-induced toxicity

Abstract

Peptides from sesame cake (PSC) were recently shown to modulate aging and oxidative stress pathways. Huntington’s disease is characterized by the hallmark presence of expanded polyglutamine (polyQ) tracts. To study the effects of PSC on polyQ-induced toxicity and possible underlying molecular mechanisms, we employed two transgenic Caenorhabditis elegans (C. elegans) models, AM140 and HA759, which respectively express polyQ expansions in muscle cells and ASH neurons. PSC extended lifespan and alleviated polyQ-induced toxicity in these nematodes. Strikingly, PSC not only decreased polyQ aggregation, but also reduced polyQ-mediated neuronal death and behavioral dysfunction in ASH neurons. Moreover, PSC increased oxidative stress resistance and restored functional parameters of mitochondria. RNA interference assays demonstrated that the beneficial effects of PSC were dependent on SKN-1. Further mechanism study showed skn-1 activation was dependent on p38 MAPK signaling pathway. These results suggest that PSC might be used as nutraceuticals to prevent and improve polyQ-related neurodegenerative disorders.