Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aβ_1-42 aggregation

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) aggregation.
• Polyphenols like Oleuropein aglycone (OleA) and Hydroxythyrosol (HT) in extra virgin olive oil (EVOO) show potential in interfering with amyloid pathways.
• The precise molecular mechanisms of their anti-amyloid effects remain largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanisms by which OleA and Hydroxythyrosol (HT) modulate Aβ1-42 fibrillation.
• To investigate the impact of these EVOO polyphenols on the formation of toxic amyloid oligomers and fibrils.
• To assess the effects of OleA and HT on Aβ aggregate/membrane interactions in neuronal cells.

Main Methods:

• Utilized a comprehensive biophysical approach.
• Employed cell biology techniques.
• Investigated interactions with Aβ1-42 peptides and human neuroblastoma SH-SY5Y cells.

Main Results:

• Oleuropein aglycone (OleA) inhibits the growth of toxic Aβ1-42 oligomers and prevents their progression into mature fibrils by interacting with the peptide's N-terminus.
• Hydroxythyrosol (HT) accelerates the formation of non-toxic Aβ fibrils.
• Both OleA and HT stabilize Aβ oligomers and fibrils, reducing their seeding activity and interaction with cell membranes.

Conclusions:

• OleA and HT exhibit distinct yet complementary mechanisms in modulating Aβ1-42 fibrillation.
• Stabilization of Aβ aggregates by these polyphenols reduces their neurotoxic potential.
• EVOO polyphenols hold significant promise for the prevention and therapeutic strategies targeting Alzheimer's disease.