Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity
| Autor: | Gunna Christiansen, Daniel E. Otzen, Hossein Mohammad-Beigi, Hoda Eskandari, Cagla Sahin, Mehdi Hosseini-Mazinani, Alireza Amiri-Nowdijeh, Nicholas P. Schafer, Jane L. Ward, Charlotte Lomax, Ian M. Møller, Dina Morshedi, Farhang Aliakbari, Ahmed F. Tawfike |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Antioxidant ALPHA-SYNUCLEIN Light medicine.medical_treatment Protein aggregation Biochemistry Oligomer chemistry.chemical_compound olive polyphenols alpha-Synuclein/antagonists & inhibitors Iridoids Iridoids/chemistry synuclein (-synuclein) biology neurodegeneration amyloid ASSOCIATION PHENOLIC-COMPOUNDS OIL CONFORMATION Parkinson disease Olea Protein Structure and Folding alpha-Synuclein Chromatography Gel Cell Survival/drug effects Olea/chemistry Cell Survival Iridoid Glucosides Protein Aggregates/drug effects Fibril oligomerization protein aggregation Protein Aggregates Structure-Activity Relationship 03 medical and health sciences α-synuclein ADHERENCE POLYPHENOLS Oleuropein Mediterranean diet Cell Line Tumor medicine Humans Molecular Biology Dose-Response Relationship Drug 030102 biochemistry & molecular biology Cell Biology AGGREGATION biology.organism_classification cell toxicity 030104 developmental biology Aglycone Fruit/chemistry chemistry Polyphenol Fruit membrane permeabilization |
| Zdroj: | Mohammad-Beigi, H, Aliakbari, F, Sahin, C, Lomax, C, Tawfike, A, Schafer, N P, Amiri-Nowdijeh, A, Eskandari, H, Møller, I M, Hosseini-Mazinani, M, Christiansen, G, Ward, J L, Morshedi, D & Otzen, D E 2019, ' Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity ' The Journal of biological chemistry . https://doi.org/10.1074/jbc.RA118.005723 Mohammad-Beigi, H, Aliakbari, F, Sahin, C, Lomax, C, Tawfike, A, P. Schafer, N, Amiri-Nowdijeh, A, Eskandari, H, Møller, I M, Hosseini-Mazinani, M, Christiansen, G, Ward, J L, Morshedi, D & Otzen, D 2019, ' Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity ', Journal of Biological Chemistry, vol. 294, no. 11, pp. 4215-4232 . https://doi.org/10.1074/jbc.RA118.005723 |
| DOI: | 10.1074/jbc.RA118.005723 |
| Popis: | Aggregation of α-synuclein (αSN) is implicated in neuronal degeneration in Parkinson's disease and has prompted searches for natural compounds inhibiting αSN aggregation and reducing its tendency to form toxic oligomers. Oil from the olive tree (Olea europaea L.) represents the main source of fat in the Mediterranean diet and contains variable levels of phenolic compounds, many structurally related to the compound oleuropein. Here, using αSN aggregation, fibrillation, size-exclusion chromatography-multi-angle light scattering (SEC-MALS)-based assays, and toxicity assays, we systematically screened the fruit extracts of 15 different olive varieties to identify compounds that can inhibit αSN aggregation and oligomer toxicity and also have antioxidant activity. Polyphenol composition differed markedly among varieties. The variety with the most effective antioxidant and -aggregation activities, Koroneiki, combined strong inhibition of αSN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic αSN oligomers. Fractionation of the Koroneiki extract identified oleuropein aglycone, hydroxy oleuropein aglycone, and oleuropein as key compounds responsible for the differences in inhibition across the extracts. These phenolic compounds inhibited αSN amyloidogenesis by directing αSN monomers into small αSN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences in the level of effective phenolic compounds in different olive varieties, insights that have implications for long-term human health. |
| Databáze: | OpenAIRE |
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