Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Alzheimer Disease*/metabolism ; Neurotoxicity Syndromes*; Amyloid beta-Peptides/chemistry ; Antibodies ; Epitopes ; Humans ; Peptide Fragments/chemistry

Soluble aggregation of amyloid β-peptide 1-42 (Aβ42) and deposition of Aβ42 aggregates are the initial pathological hallmarks of Alzheimer's disease (AD). The bipolar nature of Aβ42 molecule results in its ability to assemble into distinct oligomers and higher aggregates, which may drive some of the phenotypic heterogeneity observed in AD. Agents targeting Aβ42 or its aggregates, such as anti-Aβ42 antibodies, can inhibit the aggregation of Aβ42 and toxicity of Aβ42 aggregates to neural cells to a certain extent. However, the epitope specificity of an antibody affects its binding affinity for different Aβ42 species. Different antibodies target different sites on Aβ42 and thus elicit different neuroprotective or cytoprotective effects. In the present review, we summarize significant information reflected by anti-Aβ42 antibodies in different immunotherapies and propose an overview of the structure (conformation)-toxicity relationship of Aβ42 aggregates. This review aimed to provide a reference for the directional design of antibodies against the most pathogenic conformation of Aβ42 aggregates.

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31970883 National Natural Science Foundation of China Program

Keywords: Alzheimer’s disease (AD); aggregation; amyloid β-protein (Aβ); antibody; neurotoxicity

0 (Amyloid beta-Peptides)
0 (Antibodies)
0 (Epitopes)
0 (Peptide Fragments)

Date Created: 20221014 Date Completed: 20221017 Latest Revision: 20221019

20221213

PMC9570743

10.3390/molecules27196751

36235284