Amyloid-beta peptide dimers undergo a random coil to beta-sheet transition in the aqueous phase but not at the neuronal membrane

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00124309" target="_blank" >RIV/00216224:14740/21:00124309 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.pnas.org/content/118/39/e2106210118" target="_blank" >https://www.pnas.org/content/118/39/e2106210118</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1073/pnas.2106210118" target="_blank" >10.1073/pnas.2106210118</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Amyloid-beta peptide dimers undergo a random coil to beta-sheet transition in the aqueous phase but not at the neuronal membrane

Popis výsledku v původním jazyce

Mounting evidence suggests that the neuronal cell membrane is the main site of oligomer-mediated neuronal toxicity of amyloid-beta peptides in Alzheimer's disease. To gain a detailed understanding of the mutual interference of amyloid-beta oligomers and the neuronal membrane, we carried out microseconds of all-atom molecular dynamics (MD) simulations on the dimerization of amyloid-beta (A beta)42 in the aqueous phase and in the presence of a lipid bilayer mimicking the in vivo composition of neuronal membranes. The dimerization in solution is characterized by a random coil to beta-sheet transition that seems on pathway to amyloid aggregation, while the interactions with the neuronal membrane decrease the order of the A beta 42 dimer by attenuating its propensity to form a beta-sheet structure. The main lipid interaction partners of A beta 42 are the surface-exposed sugar groups of the gangliosides GM1. As the neurotoxic activity of amyloid oligomers increases with oligomer order, these results suggest that GM1 is neuroprotective against A beta-mediated toxicity.

Název v anglickém jazyce

Amyloid-beta peptide dimers undergo a random coil to beta-sheet transition in the aqueous phase but not at the neuronal membrane

Popis výsledku anglicky

Mounting evidence suggests that the neuronal cell membrane is the main site of oligomer-mediated neuronal toxicity of amyloid-beta peptides in Alzheimer's disease. To gain a detailed understanding of the mutual interference of amyloid-beta oligomers and the neuronal membrane, we carried out microseconds of all-atom molecular dynamics (MD) simulations on the dimerization of amyloid-beta (A beta)42 in the aqueous phase and in the presence of a lipid bilayer mimicking the in vivo composition of neuronal membranes. The dimerization in solution is characterized by a random coil to beta-sheet transition that seems on pathway to amyloid aggregation, while the interactions with the neuronal membrane decrease the order of the A beta 42 dimer by attenuating its propensity to form a beta-sheet structure. The main lipid interaction partners of A beta 42 are the surface-exposed sugar groups of the gangliosides GM1. As the neurotoxic activity of amyloid oligomers increases with oligomer order, these results suggest that GM1 is neuroprotective against A beta-mediated toxicity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Proceedings of the National Academy of Sciences of the United States of America

ISSN

0027-8424

e-ISSN

—

Svazek periodika

118

Číslo periodika v rámci svazku

39

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

„e2106210118“

Kód UT WoS článku

000708052600007

EID výsledku v databázi Scopus

2-s2.0-85115315726