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

Hossein Mohammad-Beigi; Farhang Aliakbari; Cagla Sahin; Charlotte Lomax; Ahmed Tawfike; Nicholas P. Schafer; Alireza Amiri-Nowdijeh; Hoda Eskandari; Ian Max Møller; Mehdi Hosseini-Mazinani; Gunna Christiansen; Jane L Ward; Dina Morshedi; Daniel Otzen

doi:10.1074/jbc.RA118.005723

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

Hossein Mohammad-Beigi, Farhang Aliakbari, Cagla Sahin, Charlotte Lomax, Ahmed Tawfike, Nicholas P. Schafer, Alireza Amiri-Nowdijeh, Hoda Eskandari, Ian Max Møller, Mehdi Hosseini-Mazinani, Gunna Christiansen, Jane L Ward, Dina Morshedi, Daniel Otzen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

60 Citations (Scopus)

Abstract

Aggregation of -synuclein (SN) is implicated in neuronal degeneration in Parkinson’s disease and has prompted searches for natural compounds inhibiting SN 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 SN 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 SN 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 SN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic SN 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 SN amyloidogenesis by directing SN monomers into small SN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences

Original language	English
Journal	Journal of Biological Chemistry
Volume	294
Issue	11
Pages (from-to)	4215-4232
Number of pages	18
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.RA118.005723
Publication status	Published - 2019

Keywords

-synuclein (-synuclein)
ADHERENCE
AGGREGATION
ALPHA-SYNUCLEIN
ASSOCIATION
CONFORMATION
MEDITERRANEAN DIET
Mediterranean diet
OIL
PHENOLIC-COMPOUNDS
POLYPHENOLS
Parkinson disease
amyloid
cell toxicity
membrane permeabilization
neurodegeneration
oligomerization
olive polyphenols
protein aggregation
Humans
Structure-Activity Relationship
Cell Survival/drug effects
Dose-Response Relationship, Drug
Light
Olea/chemistry
Protein Aggregates/drug effects
Fruit/chemistry
alpha-Synuclein/antagonists & inhibitors
Iridoids/chemistry
Cell Line, Tumor
Chromatography, Gel

Access to Document

10.1074/jbc.RA118.005723

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422090/pdf/zbc4215.pdf

Cite this

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, 294(11), 4215-4232. https://doi.org/10.1074/jbc.RA118.005723

@article{206df5c4b1e0479aa149ada81d276d7a,

title = "Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity",

abstract = "Aggregation of -synuclein (SN) is implicated in neuronal degeneration in Parkinson{\textquoteright}s disease and has prompted searches for natural compounds inhibiting SN 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 SN 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 SN 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 SN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic SN 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 SN amyloidogenesis by directing SN monomers into small SN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences",

keywords = "-synuclein (-synuclein), ADHERENCE, AGGREGATION, ALPHA-SYNUCLEIN, ASSOCIATION, CONFORMATION, MEDITERRANEAN DIET, Mediterranean diet, OIL, PHENOLIC-COMPOUNDS, POLYPHENOLS, Parkinson disease, amyloid, cell toxicity, membrane permeabilization, neurodegeneration, oligomerization, olive polyphenols, protein aggregation, Humans, Structure-Activity Relationship, Cell Survival/drug effects, Dose-Response Relationship, Drug, Light, Olea/chemistry, Protein Aggregates/drug effects, Fruit/chemistry, alpha-Synuclein/antagonists & inhibitors, Iridoids/chemistry, Cell Line, Tumor, Chromatography, Gel",

author = "Hossein Mohammad-Beigi and Farhang Aliakbari and Cagla Sahin and Charlotte Lomax and Ahmed Tawfike and {P. Schafer}, Nicholas and Alireza Amiri-Nowdijeh and Hoda Eskandari and M{\o}ller, {Ian Max} and Mehdi Hosseini-Mazinani and Gunna Christiansen and Ward, {Jane L} and Dina Morshedi and Daniel Otzen",

year = "2019",

doi = "10.1074/jbc.RA118.005723",

language = "English",

volume = "294",

pages = "4215--4232",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

number = "11",

}

Mohammad-Beigi, H, Aliakbari, F, Sahin, C, Lomax, C, Tawfike, A, P. Schafer, N, Amiri-Nowdijeh, A, Eskandari, H , Møller, IM, Hosseini-Mazinani, M, Christiansen, G, Ward, JL, 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

Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity. / Mohammad-Beigi, Hossein; Aliakbari, Farhang; Sahin, Cagla et al.
In: Journal of Biological Chemistry, Vol. 294, No. 11, 2019, p. 4215-4232.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Oleuropein derivatives from olive fruit extracts reduce α-synuclein fibrillation and oligomer toxicity

AU - Mohammad-Beigi, Hossein

AU - Aliakbari, Farhang

AU - Sahin, Cagla

AU - Lomax, Charlotte

AU - Tawfike, Ahmed

AU - P. Schafer, Nicholas

AU - Amiri-Nowdijeh, Alireza

AU - Eskandari, Hoda

AU - Møller, Ian Max

AU - Hosseini-Mazinani, Mehdi

AU - Christiansen, Gunna

AU - Ward, Jane L

AU - Morshedi, Dina

AU - Otzen, Daniel

PY - 2019

Y1 - 2019

N2 - Aggregation of -synuclein (SN) is implicated in neuronal degeneration in Parkinson’s disease and has prompted searches for natural compounds inhibiting SN 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 SN 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 SN 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 SN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic SN 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 SN amyloidogenesis by directing SN monomers into small SN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences

AB - Aggregation of -synuclein (SN) is implicated in neuronal degeneration in Parkinson’s disease and has prompted searches for natural compounds inhibiting SN 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 SN 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 SN 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 SN fibril nucleation and elongation with strong disaggregation activity on preformed fibrils and prevented the formation of toxic SN 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 SN amyloidogenesis by directing SN monomers into small SN oligomers with lower toxicity, thereby suppressing the subsequent fibril growth phase. Our results highlight the molecular consequences of differences

KW - -synuclein (-synuclein)

KW - ADHERENCE

KW - AGGREGATION

KW - ALPHA-SYNUCLEIN

KW - ASSOCIATION

KW - CONFORMATION

KW - MEDITERRANEAN DIET

KW - Mediterranean diet

KW - OIL

KW - PHENOLIC-COMPOUNDS

KW - POLYPHENOLS

KW - Parkinson disease

KW - amyloid

KW - cell toxicity

KW - membrane permeabilization

KW - neurodegeneration

KW - oligomerization

KW - olive polyphenols

KW - protein aggregation

KW - Humans

KW - Structure-Activity Relationship

KW - Cell Survival/drug effects

KW - Dose-Response Relationship, Drug

KW - Light

KW - Olea/chemistry

KW - Protein Aggregates/drug effects

KW - Fruit/chemistry

KW - alpha-Synuclein/antagonists & inhibitors

KW - Iridoids/chemistry

KW - Cell Line, Tumor

KW - Chromatography, Gel

U2 - 10.1074/jbc.RA118.005723

DO - 10.1074/jbc.RA118.005723

M3 - Journal article

C2 - 30655291

SN - 0021-9258

VL - 294

SP - 4215

EP - 4232

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 11

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this