scholarly journals Epitope Mapping Immunoassay Analysis of the Interaction between β-Amyloid and Fibrinogen

2019 ◽  
Vol 20 (3) ◽  
pp. 496 ◽  
Author(s):  
Vo Van Giau ◽  
Seong An
Keyword(s):  
Mouse Models ◽  
Central Region ◽  
Epitope Mapping ◽  
Polyclonal Antibodies ◽  
Fibrin Clot ◽  
Fibrin Deposition ◽  
Therapeutic Approaches ◽  
Substantial Evidence ◽  
Blood Clots ◽  
Β Amyloid

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.

scholarly journals Biochemical and structural analysis of the interaction between β-amyloid and fibrinogen

Blood ◽  
2016 ◽  
Vol 128 (8) ◽  
pp. 1144-1151 ◽  
Author(s):  
Daria Zamolodchikov ◽  
Hanna E. Berk-Rauch ◽  
Deena A. Oren ◽  
Daniel S. Stor ◽  
Pradeep K. Singh ◽  
...  
Keyword(s):  
Central Region ◽  
Crystallographic Analysis ◽  
Naturally Occurring ◽  
Fibrinogen Binding ◽  
Blood Clots ◽  
Structural Details ◽  
Main Protein ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Β Chain

Abstract The majority of patients with Alzheimer disease (AD) suffer from impaired cerebral circulation. Accumulating evidence suggests that fibrinogen, the main protein component of blood clots, plays an important role in this circulatory dysfunction in AD. Fibrinogen interacts with β-amyloid (Aβ), forming plasmin-resistant abnormal blood clots, and increased fibrin deposition is found in the brains of AD patients and mouse models. In this study, we investigated the biochemical and structural details of the Aβ-fibrinogen interaction. We identified the central region of Aβ42 as the most critical region for the interaction, which can be inhibited by specific antibodies against the central region of Aβ and by naturally occurring p3 peptides, Aβ17-40 and Aβ17-42. X-ray crystallographic analysis revealed that Aβ42 binding to fragment D of fibrinogen induced a structural change in the C-terminal region of the fibrinogen β-chain (β384-393). Furthermore, we identified an additional Aβ-binding site within the αC region of fibrinogen. Aβ binding to this αC region blocked plasmin-mediated fibrin cleavage at this site, resulting in the generation of increased levels of a plasmin-resistant fibrin degradation fragment. Overall, our study elucidates the Aβ-fibrinogen interaction and clarifies the mechanism by which Aβ-fibrinogen binding delays fibrinolysis by plasmin. These results may facilitate the development of effective therapeutics against the Aβ-fibrinogen interaction to treat cerebrovascular abnormalities in AD.

scholarly journals Erratum: Characterizing affinity epitopes between prion protein and β-amyloid using an epitope mapping immunoassay

2014 ◽  
Vol 46 (5) ◽  
pp. e96-e96
Author(s):  
Mino Kang ◽  
Su Yeon Kim ◽  
Seong Soo A An ◽  
Young Ran Ju
Keyword(s):  
Prion Protein ◽  
Epitope Mapping ◽  
Β Amyloid

Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction

1994 ◽  
Vol 107 (10) ◽  
pp. 2749-2760 ◽  
Author(s):  
M.J. Dobson ◽  
R.E. Pearlman ◽  
A. Karaiskakis ◽  
B. Spyropoulos ◽  
P.B. Moens
Keyword(s):  
Synaptonemal Complex ◽  
Fusion Proteins ◽  
Epitope Mapping ◽  
Core Protein ◽  
Binding Capacity ◽  
Polyclonal Antibodies ◽  
Meiotic Chromosome ◽  
Immunogold Labelling ◽  
Chromosome Disjunction ◽  
Metaphase I

We have used polyclonal antibodies against fusion proteins produced from cDNA fragments of a meiotic chromosome core protein, Cor1, and a protein present only in the synapsed portions of the cores, Syn1, to detect the occurrence and the locations of these proteins in rodent meiotic prophase chromosomes. The 234 amino acid Cor1 protein is present in early unpaired cores, in the lateral domains of the synaptonemal complex and in the chromosome cores when they separate at diplotene. A novel observation showed the presence of Cor1 axial to the metaphase I chromosomes and substantial amounts of Cor1 in association with pairs of sister centromeres. The centromere-associated Cor1 protein becomes dissociated from the centromeres at anaphase II and it is not found in mitotic metaphase centromeres. The extended presence of Cor1 suggests that it may have a role in chromosome disjunction by fastening chiasmata at metaphase I and by joining sister kinetochores, which ensures co-segregation at anaphase I. Two-colour immunofluorescence of Cor1 and Syn1 demonstrates that synapsis between homologous cores is initiated at few sites but advances rapidly relative to the establishment of new initiation sites. If the rapid advance of synapsis deters additional initiation sites between pairs of homologues, it may provide a mechanism for positive recombination interference. Immunogold epitope mapping of antibodies to four Syn1 fusion proteins places the amino terminus of Syn1 towards the centre of the synaptonemal complex while the carboxyl terminus extends well into the lateral domain of the synaptonemal complex. The Syn1 fusion proteins have a non-specific DNA binding capacity. Immunogold labelling of Cor1 antigens indicates that the lateral domain of the synaptonemal complex is about twice as wide as the apparent width of lateral elements when stained with electron-dense metal ions. Electron microscopy of shadow-cast surface-spread SCs confirms the greater width of the lateral domain. The implication of these dimensions is that the proteins that comprise the synaptic domain overlap with the protein constituents of the lateral domains of the synaptonemal complex more than was apparent from earlier observations. This arrangement suggests that direct interactions might be expected between some of the synaptonemal complex proteins.

scholarly journals Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization

Immunity ◽  
2018 ◽  
Vol 49 (2) ◽  
pp. 288-300.e8 ◽  
Author(s):  
Matteo Bianchi ◽  
Hannah L. Turner ◽  
Bartek Nogal ◽  
Christopher A. Cottrell ◽  
David Oyen ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Epitope Mapping ◽  
Polyclonal Antibodies ◽  
Hiv 1

Fibrin Networks Sustain Large Extensions Due to Unfolding Proteins

2010 ◽  
Author(s):  
Prashant K. Purohit
Keyword(s):  
Mechanical Properties ◽  
Protein Unfolding ◽  
Spatial Scales ◽  
Constitutive Models ◽  
Fibrin Clot ◽  
Matrix Proteins ◽  
Dramatic Decrease ◽  
Fiber Alignment ◽  
Fibrin Networks ◽  
Blood Clots

Blood clots and thrombi consist primarily of a mesh of branched fibers made of the protein fibrin. We show how these networks give rise to the remarkable extensibility and elasticity of blood clots by determining structural and mechanical properties of the clot at the network, fiber, and molecular levels. The force required to stretch a clot initially rises almost linearly and is accompanied by a dramatic decrease in the clot volume. These macroscopic changes are accompanied by fiber alignment and bundling following forced protein unfolding. We develop constitutive models to integrate observations at spatial scales that span six orders of magnitude and indicate that fibrin clot extensibility and shrinkage are both manifestations of protein unfolding, which is not apparent in other matrix proteins such as collagen.

Coagulation (Hemostasis and Thrombosis)

2012 ◽  
Author(s):  
Rajiv K. Pruthi
Keyword(s):  
Risk Factors ◽  
Platelet Activation ◽  
Coagulation Factors ◽  
Fibrin Clot ◽  
Coagulation System ◽  
Bleeding Disorders ◽  
Hemostatic System ◽  
Blood Clots ◽  
Anticoagulant System ◽  
Plug Formation

The coagulation system has 2 essential functions: to maintain hemostasis and to prevent and limit thrombosis. The procoagulant component of the hemostatic system prevents and controls hemorrhage. Vascular injury results in activation of hemostasis, which consists of vasospasm, platelet plug formation (platelet activation, adhesion, and aggregation), and fibrin clot formation (by activation of coagulation factors in the procoagulant system). The anticoagulant system prevents excessive formation of blood clots, and the fibrinolytic system breaks down and remodels blood clots. Quantitative abnormalities (deficiencies) and qualitative abnormalities of platelets and coagulation factors lead to bleeding disorders, whereas deficiencies of the anticoagulant system are risk factors for thrombosis. Common disorders of hemostasis and thrombosis are reviewed.

scholarly journals Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic Spectrum

2016 ◽  
Vol 37 (6) ◽  
pp. 609-635 ◽  
Author(s):  
Elena J. Tucker ◽  
Sonia R. Grover ◽  
Anne Bachelot ◽  
Philippe Touraine ◽  
Andrew H. Sinclair
Keyword(s):  
Mouse Models ◽  
Genetic Basis ◽  
Current Knowledge ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Activity ◽  
Substantial Evidence ◽  
Ovarian Insufficiency ◽  
Phenotypic Spectrum ◽  
Disease Mechanisms

Abstract Premature ovarian insufficiency (POI) is one form of female infertility, defined by loss of ovarian activity before the age of 40 and characterized by amenorrhea (primary or secondary) with raised gonadotropins and low estradiol. POI affects up to one in 100 females, including one in 1000 before the age of 30. Substantial evidence suggests a genetic basis for POI; however, the majority of cases remain unexplained, indicating that genes likely to be associated with this condition are yet to be discovered. This review discusses the current knowledge of the genetic basis of POI. We highlight genes typically known to cause syndromic POI that can be responsible for isolated POI. The role of mouse models in understanding POI pathogenesis is discussed, and a thorough list of candidate POI genes is provided. Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.

Dynamics of Aβ Turnover and Deposition in Different β-Amyloid Precursor Protein Transgenic Mouse Models Following γ-Secretase Inhibition

2008 ◽  
Vol 327 (2) ◽  
pp. 411-424 ◽  
Author(s):  
Dorothee Abramowski ◽  
Karl-Heinz Wiederhold ◽  
Ulrich Furrer ◽  
Anne-Lise Jaton ◽  
Anton Neuenschwander ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Precursor Protein ◽  
Transgenic Mouse Models ◽  
Β Amyloid
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