Amyloid β fibril disruption by oleuropein aglycone: long-time molecular dynamics simulation to gain insight into the mechanism of action of this polyphenol from extra virgin olive oil

Simone Brogi (Lead / Corresponding author), Hajar Sirous, Vincenzo Calderone (Lead / Corresponding author), Giulia Chemi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

In the central nervous system (CNS), extra virgin olive oil (EVOO) produces interesting effects against neurodegenerative disorders including Alzheimer's disease (AD). The valuable properties of EVOO are largely ascribed to oleuropein aglycone (OA), its most abundant phenolic constituent. In particular, it has been demonstrated that in AD, OA produces strong neuroprotective effects being able to reduce amyloid ß (Aß) aggregates, thereby diminishing the related cytotoxicity and inflammation. OA prevents Aß aggregation, but more importantly OA was able to disrupt the preformed Aß fibrils. Herein, we describe a comprehensive computational investigation of the mechanism of action of OA as an Aß fibril disruptor at the molecular level. We employed extensive molecular docking calculations and long-time molecular dynamics simulation for mimicking the system of OA/Aß fibrils. The results showed that OA is able to move in depth within the Aß fibrils targeting a key motif in Aß peptide, known to be relevant for stabilizing the assembled fibrils. OA causes a structural instability of preformed Aß fibrils, determining the effective Aß fibril disaggregation. Accordingly, this study highlighted the role of OA as a potent anti-amyloidogenic drug. On the other hand, our work has relevant implications for rationally designing potent multifunctional compounds acting as disease modifying anti-Alzheimer's drugs for the development of innovative anti-AD therapeutics.

Original languageEnglish
Pages (from-to)8122-8132
Number of pages11
JournalFood & Function
Volume11
Issue number9
Early online date28 Aug 2020
DOIs
Publication statusPublished - 23 Sep 2020

Fingerprint Dive into the research topics of 'Amyloid β fibril disruption by oleuropein aglycone: long-time molecular dynamics simulation to gain insight into the mechanism of action of this polyphenol from extra virgin olive oil'. Together they form a unique fingerprint.

Cite this