Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity

A - Papers appearing in refereed journals

Mohammed-Beigi, H., Aliakbari, F., Sahin, C., Lomax, C., Tawfike, A., Shafer, N.P., Amiri-Nowdijeh, A., Eskandari, E., Moller, I.M., Hosseini-Mazinani, M., Christiansen, G., Ward, J. L., Morshedi, D. and Otzen, D.E 2019. Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity. Journal of Biological Chemistry. 294, pp. 4215-4232.

AuthorsMohammed-Beigi, H., Aliakbari, F., Sahin, C., Lomax, C., Tawfike, A., Shafer, N.P., Amiri-Nowdijeh, A., Eskandari, E., Moller, I.M., Hosseini-Mazinani, M., Christiansen, G., Ward, J. L., Morshedi, D. and Otzen, D.E
Abstract

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–multiangle 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, hydroxyl 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.

Keywordsα-synuclein; amyloid; cell toxicity; Mediterranean diet;; membrane permeabilization
Year of Publication2019
JournalJournal of Biological Chemistry
Journal citation294, pp. 4215-4232
Digital Object Identifier (DOI)doi:10.1074/jbc.RA118.005723
Open accessPublished as green open access
FunderBiotechnology and Biological Sciences Research Council
Funder project or codeTPM - Tailoring Plant Metabolism - Work package 2 (WP2) - Designer Willows: high value phenolic glycosides for health and industry
Accepted author manuscript
Output statusPublished
Publication dates
Online17 Jan 2019
Publication process dates
Accepted17 Jan 2019
Copyright licenseAuthor copyright
PublisherAmerican Society for Biochemistry and Molecular Biology
ISSN0021-9258

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