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Gui, X.* ; Feng, S.* ; Li, Z.* ; Li, Y.* ; Reif, B. ; Shi, B.* ; Niu, Z.*

Liquid-liquid phase separation of amyloid-β oligomers modulates amyloid fibrils formation.

J. Biol. Chem. 299:102926 (2023)
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Soluble amyloid-β oligomers (AβOs) are proposed to instigate and mediate the pathology of Alzheimer's disease (AD), but the mechanisms involved are not clear. In this study, we reported that AβOs can undergo liquid-liquid phase separation (LLPS) to form liquid-like droplets in vitro. We determined that AβOs exhibited an α-helix conformation in a membrane-mimicking environment of sodium dodecyl sulfate (SDS). Importantly, SDS is capable of reconfiguring the assembly of different AβOs to induce their LLPS. Moreover, we found that droplet formation of AβOs was promoted by strong hydrated anions and weak hydrated cations, suggesting that hydrophobic interactions play a key role in mediating phase separation of AβOs. Finally, we observed that LLPS of AβOs can further promote Aβ to form amyloid fibrils, which can be modulated by (-)-epigallocatechin gallate (EGCG). Our study highlights amyloid oligomers as an important entity involved in protein liquid-to-solid phase transition and reveals the regulatory role of LLPS underlying amyloid protein aggregation, which may be relevant to the pathological process of AD.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Alzheimer’s Disease ; Amyloid-β Oligomers ; Liquid-liquid Phase Separation ; Oligomerization ; Protein Aggregation; Alzheimers-disease; Protein
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Journal Journal of Biological Chemistry, The
Quellenangaben Volume: 299, Issue: 3, Pages: , Article Number: 102926 Supplement: ,
Publisher American Society for Biochemistry and Molecular Biology
Publishing Place Radarweg 29, 1043 Nx Amsterdam, Netherlands
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Grants Henan University
NHMRC Investigator Grant
National Key Technologies R&D Program of China
National Natural Science Foundation of China