The inhibitory potential of EGCG and DMSO on tyrosine self-assembly using a yeast model for Tyrosinemia

Inborn Errors of Metabolism (IEM) disorders comprise a group of genetic and rare diseases in which there are abnormalities with the metabolism of a given metabolite (specific to each disease). Recently, our lab had discovered that a group of metabolites involved in IEM disorders are able to form amyloid assemblies that are very similar to the well-known amyloid structures formed by proteins and peptides and involved in neurodegenerative diseases. Among such metabolites is the tyrosine amino acid. Tyrosine is involved in the tyrosinemia IEM, in which patients’ cells are not able to break down tyrosine. The etiology of this disease is mostly unknown and the main treatment is a diet in which patients refrain from consuming tyrosine. A yeast model for Tyrosinemia, established by Hanaa Adsi, was used for this study. In this model sensitivity to tyrosine feeding can be observed and amyloid-like assemblies are accumulated. We studied (both in vitro and in vivo) the influence of different compounds from groups of compounds that are known to inhibit the formation of protein amyloid assemblies, such as polyphenols and chemical chaperons. Using fluorescence assays, we found the DMSO chemical chaperon as a successful in vitro inhibitor. Furthermore, we suggest the polyphenol EGCG as an efficient in vivo inhibitor that protects cells from the amyloid assemblies’ toxicity. Our study sets ground for further studies on the involvement of amyloid assemblies in IEM disorders and suggests a new approach towards finding treatment.