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Biochim Biophys Acta Gen Subj. 2018 Jun;1862(6):1432-1442. doi: 10.1016/j.bbagen.2018.03.023. Epub 2018 Mar 21.

Oleuropein aglycone: A polyphenol with different targets against amyloid toxicity.

Author information

1
Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni, 50 50134 Florence, Italy; Department of Neuroscience, Psychology, Area of Medicine and Health of the Child of the University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy.
2
Department of Physics, University of Genova, via Dodecaneso 33, 16146, Genova, Italy.
3
Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Viale Taramelli 3/B, 27100 Pavia, Italy.
4
Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Viale Taramelli 3/B, 27100 Pavia, Italy; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine Royal Free Campus, University College London, NW3 2PF London, UK.
5
Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni, 50 50134 Florence, Italy.
6
Department of Molecular Medicine, Institute of Biochemistry, University of Pavia, Viale Taramelli 3/B, 27100 Pavia, Italy; Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine Royal Free Campus, University College London, NW3 2PF London, UK; Interuniversity Center for the Study of Neurodegenerative Diseases (CIMN), Florence, Italy.
7
Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni, 50 50134 Florence, Italy; Interuniversity Center for the Study of Neurodegenerative Diseases (CIMN), Florence, Italy.
8
Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni, 50 50134 Florence, Italy; Interuniversity Center for the Study of Neurodegenerative Diseases (CIMN), Florence, Italy. Electronic address: monica.bucciantini@unifi.it.

Abstract

BACKGROUND:

Many data highlight the benefits of the Mediterranean diet and its main lipid component, extra-virgin olive oil (EVOO). EVOO contains many phenolic compounds that have been found effective against several aging- and lifestyle-related diseases, including neurodegeneration. Oleuropein, a phenolic secoiroid glycoside, is the main polyphenol in the olive oil. It has been reported that the aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid aggregation of a number of proteins/peptides involved in amyloid, particularly neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying protection against cognitive deterioration.

METHODS:

In this study, we carried out a cellular and biophysical study on the relationships between the effects of OleA on the aggregation and cell interactions of the D76N β2-microglobulin (D76N b2m) variant associated with a familial form of systemic amyloidosis with progressive bowel dysfunction and extensive visceral amyloid deposits.

RESULTS:

Our results indicate that OleA protection against D76N b2m cytotoxicity results from i) a modification of the conformational and biophysical properties of its amyloid fibrils; ii) a modification of the cell bilayer surface properties of exposed cells.

CONCLUSIONS:

This study reveals that OleA remodels not only D76N b2m aggregates but also the cell membrane interfering with the misfolded proteins-cell membrane association, in most cases an early event triggering amyloid-mediated cytotoxicity.

GENERAL SIGNIFICANCE:

The data provided in the present article focus on OleA protection, featuring this polyphenol as a promising plant molecule useful against amyloid diseases.

KEYWORDS:

Amyloid; D76N variant; Oleuropein aglycone; β2-microglobulin

PMID:
29571746
DOI:
10.1016/j.bbagen.2018.03.023
[Indexed for MEDLINE]

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