Modulating Aβ aggregation by tyrosol-based ligands: The crucial role of the catechol moiety

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00531510" target="_blank" >RIV/61388963:_____/20:00531510 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.bpc.2020.106434" target="_blank" >https://doi.org/10.1016/j.bpc.2020.106434</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bpc.2020.106434" target="_blank" >10.1016/j.bpc.2020.106434</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Modulating Aβ aggregation by tyrosol-based ligands: The crucial role of the catechol moiety

Popis výsledku v původním jazyce

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 Aβ1–40 aggregation are ascribable to their capacity to arrange H-bonds network between the ligand (position C-3) and the peptide (Glu22). We believe that our results may contribute to the design of more effective and safe small molecules able to contrast pathogenic amyloid aggregation

Název v anglickém jazyce

Modulating Aβ aggregation by tyrosol-based ligands: The crucial role of the catechol moiety

Popis výsledku anglicky

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 Aβ1–40 aggregation are ascribable to their capacity to arrange H-bonds network between the ligand (position C-3) and the peptide (Glu22). We believe that our results may contribute to the design of more effective and safe small molecules able to contrast pathogenic amyloid aggregation

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biophysical Chemistry

ISSN

0301-4622

e-ISSN

—

Svazek periodika

265

Číslo periodika v rámci svazku

Oct

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

7

Strana od-do

106434

Kód UT WoS článku

000566472600001

EID výsledku v databázi Scopus

2-s2.0-85088089692