Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aβ1-42 aggregation

Food Chem Toxicol. 2019 Jul:129:1-12. doi: 10.1016/j.fct.2019.04.015. Epub 2019 Apr 14.

Abstract

Oleuropein aglycone (OleA), the most abundant polyphenol in extra virgin olive oil (EVOO), and Hydroxythyrosol (HT), the OleA main metabolite, have attracted our interest due to their multitarget effects, including the interference with amyloid aggregation path. However, the mechanistic details of their anti-amyloid effect are not known yet. We report here a broad biophysical approach and cell biology techniques that enabled us to characterize the different molecular mechanisms by which OleA and HT modulate the Aβ1-42 fibrillation, a main histopathological feature of Alzheimer's disease (AD). In particular, OleA prevents the growth of toxic Aβ1-42 oligomers and blocks their successive growth into mature fibrils following its interaction with the peptide N-terminus, while HT speeds up harmless fibril formation. Our data demonstrate that, by stabilizing oligomers and fibrils, both polyphenols reduce their seeding activity and aggregate/membrane interaction on human neuroblastoma SH-SY5Y cells. These findings highlight the great potential of EVOO polyphenols and offer the possibility to validate and to optimize their use for possible AD prevention and therapy.

Keywords: Acrylamide (PubChem CID: 6579); Alzheimer's disease; Amyloid; Aβ(1-42) peptide; Congo Red (PubChem CID: 11313); Hydroxythyrosol (PubChem: 82755) Dimethylsulfoxide (PubChem CID: 679); Hydroxytyrosol; MTT (PubChem CID: 64965); N,N-dimethylformamide (PubChem CID: 6228); Oleuropein Aglycone (PubChem CID: 56842347); Oleuropein aglycone; Sodium Dodecil Sulfate (PubChem CID: 3423265).

MeSH terms

  • Acetates / pharmacology*
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / toxicity
  • Biophysical Phenomena
  • Cell Line, Tumor
  • Cyclopentane Monoterpenes
  • Humans
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Oxidative Stress
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / metabolism
  • Peptide Fragments / toxicity
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology
  • Pyrans / pharmacology*

Substances

  • Acetates
  • Amyloid beta-Peptides
  • Cyclopentane Monoterpenes
  • Peptide Fragments
  • Pyrans
  • amyloid beta-protein (1-42)
  • oleuropein aglycone
  • 3,4-dihydroxyphenylethanol
  • Phenylethyl Alcohol