Modulating Aβ aggregation by tyrosol-based ligands: The crucial role of the catechol moiety.
Alzheimer's disease
Aβ anti-aggregation
Homovanillyl alcohol
Hydroxytyrosol
Tyrosol
Journal
Biophysical chemistry
ISSN: 1873-4200
Titre abrégé: Biophys Chem
Pays: Netherlands
ID NLM: 0403171
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
07
04
2020
revised:
30
06
2020
accepted:
12
07
2020
pubmed:
25
7
2020
medline:
11
5
2021
entrez:
25
7
2020
Statut:
ppublish
Résumé
The abnormal deposition of Aβ amyloid deposits in the brain is a hallmark of Alzheimer's disease (AD). Based on this evidence, many current therapeutic approaches focus on the development of small molecules halting Aβ aggregation. However, due to the temporary and elusive structures of amyloid assemblies, the rational design of aggregation inhibitors remains a challenging task. Here we combine ThT assays and MD simulations to study Aβ aggregation in the presence of the natural compounds tyrosol (TY), 3-hydroxytyrosol (HDT), and 3-methoxytyrosol (homovanillyl alcohol - HVA). We show that albeit HDT is a potent inhibitor of amyloid growth, TY and HVA catalyze fibril formation. An inspection of MD simulations trajectories revealed that the different effects of these three molecules on Aβ
Identifiants
pubmed: 32707474
pii: S0301-4622(20)30142-3
doi: 10.1016/j.bpc.2020.106434
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Catechols
0
Ligands
0
Peptide Fragments
0
amyloid beta-protein (1-40)
0
amyloid beta-protein (1-42)
0
homovanillic alcohol
0
4-hydroxyphenylethanol
1AK4MU3SNX
catechol
LF3AJ089DQ
Phenylethyl Alcohol
ML9LGA7468
Homovanillic Acid
X77S6GMS36
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106434Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.