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

Simple item page
dc.citation.firstpage4215en_US
dc.citation.issueNumber11en_US
dc.citation.journalTitleJournal of Biological Chemistryen_US
dc.citation.lastpage4232en_US
dc.citation.volumeNumber294en_US
dc.contributor.authorMohammad-Beigi, Hosseinen_US
dc.contributor.authorAliakbari, Farhangen_US
dc.contributor.authorSahin, Caglaen_US
dc.contributor.authorLomax, Charlotteen_US
dc.contributor.authorTawfike, Ahmeden_US
dc.contributor.authorSchafer, Nicholas P.en_US
dc.contributor.authorAmiri-Nowdijeh, Alirezaen_US
dc.contributor.authorEskandari, Hodaen_US
dc.contributor.authorMøller, Ian Maxen_US
dc.contributor.authorHosseini-Mazinani, Mehdien_US
dc.contributor.authorChristiansen, Gunnaen_US
dc.contributor.authorWard, Jane L.en_US
dc.contributor.authorMorshedi, Dinaen_US
dc.contributor.authorOtzen, Daniel E.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2021-10-07T18:33:06Zen_US
dc.date.available2021-10-07T18:33:06Zen_US
dc.date.issued2019en_US
dc.description.abstractAggregation 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.en_US
dc.identifier.citationMohammad-Beigi, Hossein, Aliakbari, Farhang, Sahin, Cagla, et al.. "Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity." <i>Journal of Biological Chemistry,</i> 294, no. 11 (2019) Elsevier: 4215-4232. https://doi.org/10.1074/jbc.RA118.005723.en_US
dc.identifier.digitalPIIS0021925820418289en_US
dc.identifier.doihttps://doi.org/10.1074/jbc.RA118.005723en_US
dc.identifier.urihttps://hdl.handle.net/1911/111521en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsCreative Commons Attribution (CC BY 4.0)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleOleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicityen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
PIIS0021925820418289.pdf
Size:
6.05 MB
Format:
Adobe Portable Document Format
Download
Collections
Faculty Publications
Chemistry Publications