The Inhibitory Effects of Cuminaldehyde on Amyloid Fibrillation and Cytotoxicity of Alpha-synuclein | ||
| Pathobiology Reserach | ||
| Article 5, Volume 15, Issue 1, 2012, Pages 45-60 PDF (2.64 M) | ||
| Authors | ||
| Dina Morshedi* ; Farhang Aliakbari | ||
| National Institute of Genetic Engineering and Biotechnology, Tehran, Iran | ||
| Abstract | ||
| 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. | ||
| Keywords | ||
| Alpha-synuclein; Cuminaldehyde; Fibril inhibitor; Parkinson’s | ||
| References | ||
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