Epitope Mapping Immunoassay Analysis of the Interaction between ß-Amyloid and Fibrinogen.
Int J Mol Sci
; 20(3)2019 Jan 24.
Article
em En
| MEDLINE
| ID: mdl-30678343
ABSTRACT
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 ß-amyloid (1-42) (Aß), 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 Aß. We discovered the Aß5â»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 Aß. Aß 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 Aßâ»Fbg interaction that may involve the mechanism by which Aßâ»Fbg binding delays fibrinolysis by plasmin, providing valuable information in the development of therapeutic approaches for AD.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fibrinogênio
/
Peptídeos beta-Amiloides
/
Mapeamento de Epitopos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article