Inhibitory effect of Euphorbia tannins on α-synuclein aggregation in aqueous solutions

Forming of neurotoxic aggregates of a small neuronal protein - alpha-synuclein (ASN) - is considered one of the main reasons of pathogenesis of Parkinson's disease (PD). ASN is a small protein with the ability to forms fibrils and insoluble Lewy bodies responsible for disruption of neuronal functions. Inhibition of protein aggregation to eliminate the formation of insoluble aggregates is one of strategies to prevent the development of neurological syndromes. Despite many investigations, there is a lack of effective drugs against neurodegenerative diseases. In this study the influence of 2 tannins: flexible 1,3,6-tri-O-galloyl-β-d-glucose (T1) and stiff 1-O-galloyl-2,3-hexahydroxydiphenoyl-4,6-valoneoyl-β-d-glucose (T2), on α-synuclein aggregation has been investigated. Studies with thioflavin T have demonstrated that both tannins strongly inhibited ASN aggregation. Fluorescence measurements showed that both bind to ASN, forming complexes. Isothermal titration calorimetry showed binding to ASN was an exothermic reaction. Circular dichroism results showed the influence of our compounds on ASN secondary structure. It can be concluded that these 2 tannins have a strong ability to interact with α-synuclein and inhibit their aggregation. [Display omitted] •Euphorbia tannins form complexes with α-synuclein.•Euphorbia tannins very strong inhibit α-synuclein oligomerization.•Interaction between Euphorbia tannins and α-synuclein is exothermic.