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Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen
The vast majority of patients with Alzheimer’s disease (AD) suffer from impaired cerebral circulation. Substantial evidence indicates that fibrinogen (Fbg) and fibrin clot formation play an important role in this circulatory dysfunction in AD. Fbg interacts with β-amyloid (1-42) (Aβ), forming plasmi...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387197/ https://www.ncbi.nlm.nih.gov/pubmed/30678343 http://dx.doi.org/10.3390/ijms20030496 |
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author | Van Giau, Vo An, Seong Soo A. |
author_facet | Van Giau, Vo An, Seong Soo A. |
author_sort | Van Giau, Vo |
collection | PubMed |
description | The vast majority of patients with Alzheimer’s disease (AD) suffer from impaired cerebral circulation. Substantial evidence indicates that fibrinogen (Fbg) and fibrin clot formation play an important role in this circulatory dysfunction in AD. Fbg interacts with β-amyloid (1-42) (Aβ), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition has been discovered in the brains of AD patients and mouse models. In this study, biochemical approaches and the epitope mapping immunoassay were employed to characterize binding epitopes within the Fbg and complementary epitopes in Aβ. We discovered the Aβ5–25 peptide as the most critical region for the interaction, which can be inhibited by specific monoclonal and polyclonal antibodies against the central region of Aβ. Aβ binding to Fbg may block plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of plasmin-resistant fibrin degradation fragments. Our study elucidates the Aβ–Fbg interaction that may involve the mechanism by which Aβ–Fbg binding delays fibrinolysis by plasmin, providing valuable information in the development of therapeutic approaches for AD. |
format | Online Article Text |
id | pubmed-6387197 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63871972019-02-27 Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen Van Giau, Vo An, Seong Soo A. Int J Mol Sci Article The vast majority of patients with Alzheimer’s disease (AD) suffer from impaired cerebral circulation. Substantial evidence indicates that fibrinogen (Fbg) and fibrin clot formation play an important role in this circulatory dysfunction in AD. Fbg interacts with β-amyloid (1-42) (Aβ), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition has been discovered in the brains of AD patients and mouse models. In this study, biochemical approaches and the epitope mapping immunoassay were employed to characterize binding epitopes within the Fbg and complementary epitopes in Aβ. We discovered the Aβ5–25 peptide as the most critical region for the interaction, which can be inhibited by specific monoclonal and polyclonal antibodies against the central region of Aβ. Aβ binding to Fbg may block plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of plasmin-resistant fibrin degradation fragments. Our study elucidates the Aβ–Fbg interaction that may involve the mechanism by which Aβ–Fbg binding delays fibrinolysis by plasmin, providing valuable information in the development of therapeutic approaches for AD. MDPI 2019-01-24 /pmc/articles/PMC6387197/ /pubmed/30678343 http://dx.doi.org/10.3390/ijms20030496 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Van Giau, Vo An, Seong Soo A. Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen |
title | Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen |
title_full | Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen |
title_fullStr | Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen |
title_full_unstemmed | Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen |
title_short | Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen |
title_sort | epitope mapping immunoassay analysis of the interaction between β-amyloid and fibrinogen |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387197/ https://www.ncbi.nlm.nih.gov/pubmed/30678343 http://dx.doi.org/10.3390/ijms20030496 |
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