Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/19/6751 |
| _version_ | 1827653634706374656 |
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| author | Chuli Song Tianyu Zhang Yingjiu Zhang |
| author_facet | Chuli Song Tianyu Zhang Yingjiu Zhang |
| author_sort | Chuli Song |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T21:22:31Z |
| format | Article |
| id | doaj.art-2e1be1aaf0c64670a9db195c7ed1525b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:22:31Z |
| publishDate | 2022-10-01 |
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| series | Molecules |
| spelling | doaj.art-2e1be1aaf0c64670a9db195c7ed1525b2023-11-23T21:16:39ZengMDPI AGMolecules1420-30492022-10-012719675110.3390/molecules27196751Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42Chuli Song0Tianyu Zhang1Yingjiu Zhang2Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, ChinaKey Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, ChinaKey Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, ChinaSoluble 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.https://www.mdpi.com/1420-3049/27/19/6751Alzheimer’s disease (AD)amyloid β-protein (Aβ)neurotoxicityantibodyaggregation |
| spellingShingle | Chuli Song Tianyu Zhang Yingjiu Zhang Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42 Molecules Alzheimer’s disease (AD) amyloid β-protein (Aβ) neurotoxicity antibody aggregation |
| title | Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42 |
| title_full | Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42 |
| title_fullStr | Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42 |
| title_full_unstemmed | Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42 |
| title_short | Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42 |
| title_sort | conformational essentials responsible for neurotoxicity of aβ42 aggregates revealed by antibodies against oligomeric aβ42 |
| topic | Alzheimer’s disease (AD) amyloid β-protein (Aβ) neurotoxicity antibody aggregation |
| url | https://www.mdpi.com/1420-3049/27/19/6751 |
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