Lipid membranes induce structural conversion from amyloid oligomers to fibrils.

Lei Gu, Zhefeng Guo

Biochemical and biophysical research communications 2021 Jun 11

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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. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Lei Gu, Zhefeng Guo. Lipid membranes induce structural conversion from amyloid oligomers to fibrils. Biochemical and biophysical research communications. 2021 Jun 11;557:122-126