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

Aggregation mechanisms and molecular structures of amyloid-β in Alzheimer's disease.

Chem. Eur. J. 30:e202400277 (2024)
Publ. Version/Full Text DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Amyloid plaques are a major pathological hallmark involved in Alzheimer's disease and consist of deposits of the amyloid-β peptide (Aβ). The aggregation process of Aβ is highly complex, which leads to polymorphous aggregates with different structures. In addition to aberrant aggregation, Aβ oligomers can undergo liquid-liquid phase separation (LLPS) and form dynamic condensates. It has been hypothesized that these amyloid liquid droplets affect and modulate amyloid fibril formation. In this review, we briefly introduce the relationship between stress granules and amyloid protein aggregation that is associated with neurodegenerative diseases. Then we highlight the regulatory role of LLPS in Aβ aggregation and discuss the potential relationship between Aβ phase transition and aggregation. Furthermore, we summarize the current structures of Aβ oligomers and amyloid fibrils, which have been determined using nuclear magnetic resonance (NMR) and cryo-electron microscopy (cryo-EM). The structural variations of Aβ aggregates provide an explanation for the different levels of toxicity, shed light on the aggregation mechanism and may pave the way towards structure-based drug design for both clinical diagnosis and treatment.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Alzheimer's Disease ; Amyloid-β Peptide ; Liquid-liquid Phase Separation ; Protein Aggregation ; Solid-state Nmr; Liquid Phase-separation; Fibril Structure; Atomic Structures; Stress Granules; Alpha-synuclein; A-beta(1-42); Polymorphism; Peptide; Complexity; Amyloid-beta(1-42)
ISSN (print) / ISBN 0947-6539
e-ISSN 1521-3765
Journal Chemistry - A European Journal
Quellenangaben Volume: 30, Issue: 48, Pages: , Article Number: e202400277 Supplement: ,
Publisher Wiley
Publishing Place Postfach 101161, 69451 Weinheim, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
Grants Projekt DEAL
Bavarian NMR Center
Helmholtz-Gemeinschaft
German Science Foundation
National Natural Science Foundation of China