Lipid membranes induce structural conversion from amyloid oligomers to fibrils

Copyright © 2021 Elsevier Inc. All rights reserved..

Formation of amyloid oligomers and fibrils underlies the pathogenesis of a number of neurodegenerative diseases such as Alzheimer's. One mechanism of action by which Aβ aggregates cause neuronal toxicity is through interactions with cellular membranes. Aβ aggregates have been shown to disrupt membrane integrity via pore formation, membrane thinning, or lipid extraction. At the same time, lipid membranes also affect the rate of Aβ aggregation and remodel pre-formed Aβ fibrils. Here we show that Aβ42 globulomers, a type of well-characterized and stable Aβ oligomers, convert to amyloid fibrils in the presence of DOPC liposomes. Electron paramagnetic resonance studies show that the fibrils converted from Aβ42 globulomers adopt the same structure as fibrils formed directly from monomers. Our results suggest that the interactions between Aβ oligomers and cellular membranes are dynamic. By converting Aβ oligomers to fibrils, the lipid membrane can reduce the membrane-disrupting activities caused by these oligomers. Modulation of Aβ-membrane interactions as a therapeutic strategy should take into account the dynamic nature of these interactions.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:557

Enthalten in:

Biochemical and biophysical research communications - 557(2021) vom: 11. Juni, Seite 122-126

Sprache:

Englisch

Beteiligte Personen:

Gu, Lei [VerfasserIn]
Guo, Zhefeng [VerfasserIn]

Links:

Volltext

Themen:

Aβ oligomers
Alzheimer’s disease
Amyloid
Amyloid beta-Peptides
Amyloid fibrils
Amyloidogenic Proteins
Journal Article
Liposome
Liposomes
Membrane Lipids
Protein aggregation
Research Support, N.I.H., Extramural

Anmerkungen:

Date Completed 02.08.2021

Date Revised 16.07.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bbrc.2021.03.174

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM324171455