the inhibitory effects of cuminaldehyde on amyloid fibrillation and cytotoxicity of alpha-synuclein

objective: alpha-synuclein is a major component of protein plaques in synucleinopathies, particularly parkinson’s disease. the purpose of this study is to assess the inhibitory effects of cuminaldehyde on the fibrillation of alpha-synuclein. methods: alpha-synuclein was expressed in escherichia coli and subsequently purified. for the process of fibrillation, purified protein was incubated at 37◦c and ph 7.2. fibrillation was analyzed by the standard fibril methods. the effects of different concentrations of cuminaldehyde (20-500 μm) on alpha-synuclein fibrillation were studied by assessment of the cytotoxic effects of samples on the neuroblastoma cell line, sk-n-mc. to study the protein aggregation forms that were generated in the presence of cuminaldehyde, sds resistance and induced fibrillation (seeding) methods were employed. for studying its specificity on alpha-synuclein, the effect of cuminaldehyde on lysozyme fibrillation was also examined. results: we showed, for the first time, that cuminaldehyde inhibited fibrillation by more than 80%. the highest inhibition was observed at the ratio of 5-15 moles of drug to protein. the viability of the treated cells with inhibited proteins was more than 90%, whereas non-inhibited samples caused a decrease in viability by 50%. inhibited samples were not resistant to sds and they were unable to induce fibrillation. cuminaldehyde did not inhibit lysozyme fibrillation. conclusion: cuminaldehyde inhibited fibrillation of alpha-synuclein which was accompanied by small amorphous aggregated particles of alpha synuclein. the inhibited protein samples did not induce aggregation. thus, cuminaldehyde can be considered as a candidate to inhibit the formation of alpha-synuclein plaques.