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Christoph Bührer - One of the best experts on this subject based on the ideXlab platform.
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Binding of human Serum Amyloid P comPonentto L-selectin
European Journal of Immunology, 2006Co-Authors: Dietger Stibenz, Michael Gräfe, Nils Debus, Michael Hasbach, Inke Bahr, Kristof Graf, Eckart Fleck, Usan Thanabalasingam, Christoph BührerAbstract:Serum concentrations of soluble L-selectin by far exceed those of other soluble adhesion molecules, and Serum soluble L-selectin concentrations are remarkably stable uPon Prolonged storage. We Present evidence for Ca2+-dePendent binding interactions between human Serum Amyloid P (SAP), a Proteolysis-resistant Pentraxin glycoProtein, and L-selectin, as shown by surface Plasmon resonance measurements, Protein band shift assays in a native PAGE system, and after SDS-PAGE and membrane transfer. Monoclonal antibodies to L-selectin strongly reduced binding of biotinylated SAP to L-selectin-IgG chimeras immobilized on microtiter Plates. As binding was reduced by Prior glycoPePtidase F treatment of L-selectin but not of SAP, it aPPears to be based on SAP lectin domain interactions with N-linked L-selectin carbohydrates. In freshly PrePared human lymPhocytes, SAP incubation induced exPression of a β2 integrin neoePitoPe associated with high-affinity binding. This was Partially blocked by Pre-incubation with Fab fragments of two anti-L-selectin antibodies. In flow chamber exPeriments, SAP inhibited the adherence of human neutroPhils to activated endothelium under shear stress. Thus, SAP binds to human L-selectin and affects L-selectin-dePendent leukocyte-endothelial interactions.
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Binding of human Serum Amyloid P comPonentto L‐selectin
European journal of immunology, 2006Co-Authors: Dietger Stibenz, Michael Gräfe, Nils Debus, Michael Hasbach, Inke Bahr, Kristof Graf, Eckart Fleck, Usan Thanabalasingam, Christoph BührerAbstract:Serum concentrations of soluble L-selectin by far exceed those of other soluble adhesion molecules, and Serum soluble L-selectin concentrations are remarkably stable uPon Prolonged storage. We Present evidence for Ca2+-dePendent binding interactions between human Serum Amyloid P (SAP), a Proteolysis-resistant Pentraxin glycoProtein, and L-selectin, as shown by surface Plasmon resonance measurements, Protein band shift assays in a native PAGE system, and after SDS-PAGE and membrane transfer. Monoclonal antibodies to L-selectin strongly reduced binding of biotinylated SAP to L-selectin-IgG chimeras immobilized on microtiter Plates. As binding was reduced by Prior glycoPePtidase F treatment of L-selectin but not of SAP, it aPPears to be based on SAP lectin domain interactions with N-linked L-selectin carbohydrates. In freshly PrePared human lymPhocytes, SAP incubation induced exPression of a β2 integrin neoePitoPe associated with high-affinity binding. This was Partially blocked by Pre-incubation with Fab fragments of two anti-L-selectin antibodies. In flow chamber exPeriments, SAP inhibited the adherence of human neutroPhils to activated endothelium under shear stress. Thus, SAP binds to human L-selectin and affects L-selectin-dePendent leukocyte-endothelial interactions.
Tamas Pazmany - One of the best experts on this subject based on the ideXlab platform.
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Serum Amyloid P comPonent induces TUNEL-Positive nuclei in rat brain after intrahiPPocamPal administration.
Brain research, 2007Co-Authors: Zoltán Urbányi, Miklós Sass, Judit Laszy, Viktor Takács, Istvan Gyertyan, Tamas PazmanyAbstract:Serum Amyloid P comPonent (SAP)-induced neuronal aPoPtosis has been demonstrated on the Primary culture of embryonic rat cerebral cortex in vitro. Here we Present Pieces of evidence that cell death is also induced by Serum Amyloid P comPonent in living rat brain similarly to that in cell culture. IntrahiPPocamPally administered SAP diffuses from the site of injection to the cortical and subcortical area of the rat brain and enters the cells of brain tissue in 1 week. It induces elevation of the number of in situ TdT-mediated dUTP-X nick end-labeled nuclei in the hiPPocamPus, cortex and subcortical structures of rat central nervous system. DNA fragmentation, which is detected by the end labeling reaction, is characteristic to aPoPtosis. It develoPs in 4 weeks following exPosure. APoPtosis is an imPortant form of cell death in different neurodegenerative diseases including Alzheimer's disease. Our Present work reveals that aPoPtosis can be induced by SAP beyond other hitherto known aPoPtosis inducing comPonents of neurodegeneration. Hereby SAP seems to be an imPortant comPonent of the Process, which leads to exPanded neuronal loss in the Pathomechanism of neurodegenerative diseases.
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Evidence for an extended interacting surface between β-Amyloid and Serum Amyloid P comPonent
Neuroscience letters, 2006Co-Authors: István Likó, Tamas Pazmany, Marianna Mák, Éva Klement, Éva Hunyadi-gulyás, Katalin F. Medzihradszky, Zoltán UrbányiAbstract:Abstract Studying the interaction between Serum Amyloid P comPonent (SAP) and β-Amyloid (Aβ) a new Aβ binding site was identified on the SAP near the known binding site at the two bound calcium ions. SAP stabilizes dePosits in neurodegenerative diseases, which is manifested via Aβ-binding. Because the inhibition of this interaction is a Potential theraPeutic target in neurodegeneration, the structural basis of SAP-Aβ binding was studied. The chymotryPtic digestion of SAP resulted in a 18,223 Da Product identified by mass sPectrometry. This cleavage was inhibited by Aβ revealing that this cleaving site between Tyr-140 and Gly-141 is involved in the interaction between SAP and Aβ⋅ These results suggest that the Aβ-binding site on SAP is larger than it was recently assumed.
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Glycosaminoglycans inhibit neurodegenerative effects of Serum Amyloid P comPonent in vitro.
Neurochemistry international, 2005Co-Authors: Zoltán Urbányi, Erika Forrai, Miklós Sárvári, István Likó, Janos Illes, Tamas PazmanyAbstract:Abstract Serum Amyloid P comPonent, a member of Pentraxin Serum Protein family, has been suggested to contribute to the Progression of neurodegeneration including Alzheimer's disease by binding to β-Amyloid fibrils leading to an increased stability of the dePosits against Proteolytic degradation and by inducing neuronal aPoPtosis. Here, we show that glycosaminoglycans inhibit both the Serum Amyloid P comPonent–β-Amyloid interaction and the neurotoxic effect of Serum Amyloid P comPonent. These effects correlate with the structure of glycosaminoglycans and show different structure–activity relationshiP in the case of the two different effects. While the efficacy of the inhibition on the Serum Amyloid P comPonent-induced cell death increases with the uronic acid content, the inhibitory activity on the Serum Amyloid P comPonent–β-Amyloid interaction decreases with the increasing uronic acid content of the glycosaminoglycans. The inhibitory effect of glycosaminoglycans on the interaction between the first comPonent of the comPlement cascade (C1q) and β-Amyloid shows a similar structure–activity relationshiP as on the Serum Amyloid P comPonent–β-Amyloid interaction. This suggests that glycosaminoglycans interfere with the binding site on β-Amyloid for Serum Amyloid P comPonent and C1q. The functional consequence of this binding has been demonstrated by heParin which Promotes the Proteolysis of β-Amyloid in vitro in the Presence of Serum Amyloid P comPonent. Our results suggest that glycosaminoglycans might have theraPeutical Potential on the neurodegeneration reducing its Progress.
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Serum Amyloid P comPonent induces neuronal aPoPtosis and beta-Amyloid immunoreactivity.
Brain research, 2003Co-Authors: Zoltán Urbányi, Miklós Sass, Lajos László, Thomas B Tomasi, Erzsébet Tóth, Eva Mekes, Tamas PazmanyAbstract:Previously we have rePorted Serum Amyloid P comPonent (SAP) induced cell death in cerebro-cortical cultures of rat brain. In this PaPer we studied the tyPes of target cells and the molecular mechanism of SAP-induced cell death. Immuno-electron and light microscoPy revealed that SAP Penetrates the Plasma membrane and translocates selectively into the nuclei of neurons. Neuronal cells with SAP immunoreactivity exhibit the morPhological hallmarks of aPoPtosis in vitro. The aPoPtotic mechanism of cell death is also suPPorted by the increased Bax/Bcl-2 ratio. In addition to neurotoxic effects, we detected elevated beta-Amyloid (Abeta) immunoreactivity following SAP treatment. This study suPPorts the thesis that SAP Plays an imPortant role in the Pathomechanism of neurodegenerative diseases, including Alzheimer's disease by inducing neuronal aPoPtosis.
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Serum Amyloid P comPonent induces neuronal aPoPtosis and β-Amyloid immunoreactivity
Brain Research, 2003Co-Authors: Zoltán Urbányi, Miklós Sass, Lajos László, Thomas B Tomasi, Erzsébet Tóth, Eva Mekes, Tamas PazmanyAbstract:Abstract Previously we have rePorted Serum Amyloid P comPonent (SAP) induced cell death in cerebro-cortical cultures of rat brain. In this PaPer we studied the tyPes of target cells and the molecular mechanism of SAP-induced cell death. Immuno-electron and light microscoPy revealed that SAP Penetrates the Plasma membrane and translocates selectively into the nuclei of neurons. Neuronal cells with SAP immunoreactivity exhibit the morPhological hallmarks of aPoPtosis in vitro. The aPoPtotic mechanism of cell death is also suPPorted by the increased Bax/Bcl-2 ratio. In addition to neurotoxic effects, we detected elevated β-Amyloid (Aβ) immunoreactivity following SAP treatment. This study suPPorts the thesis that SAP Plays an imPortant role in the Pathomechanism of neurodegenerative diseases, including Alzheimer’s disease by inducing neuronal aPoPtosis.
Zoltán Urbányi - One of the best experts on this subject based on the ideXlab platform.
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Serum Amyloid P comPonent induces TUNEL-Positive nuclei in rat brain after intrahiPPocamPal administration.
Brain research, 2007Co-Authors: Zoltán Urbányi, Miklós Sass, Judit Laszy, Viktor Takács, Istvan Gyertyan, Tamas PazmanyAbstract:Serum Amyloid P comPonent (SAP)-induced neuronal aPoPtosis has been demonstrated on the Primary culture of embryonic rat cerebral cortex in vitro. Here we Present Pieces of evidence that cell death is also induced by Serum Amyloid P comPonent in living rat brain similarly to that in cell culture. IntrahiPPocamPally administered SAP diffuses from the site of injection to the cortical and subcortical area of the rat brain and enters the cells of brain tissue in 1 week. It induces elevation of the number of in situ TdT-mediated dUTP-X nick end-labeled nuclei in the hiPPocamPus, cortex and subcortical structures of rat central nervous system. DNA fragmentation, which is detected by the end labeling reaction, is characteristic to aPoPtosis. It develoPs in 4 weeks following exPosure. APoPtosis is an imPortant form of cell death in different neurodegenerative diseases including Alzheimer's disease. Our Present work reveals that aPoPtosis can be induced by SAP beyond other hitherto known aPoPtosis inducing comPonents of neurodegeneration. Hereby SAP seems to be an imPortant comPonent of the Process, which leads to exPanded neuronal loss in the Pathomechanism of neurodegenerative diseases.
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Evidence for an extended interacting surface between β-Amyloid and Serum Amyloid P comPonent
Neuroscience letters, 2006Co-Authors: István Likó, Tamas Pazmany, Marianna Mák, Éva Klement, Éva Hunyadi-gulyás, Katalin F. Medzihradszky, Zoltán UrbányiAbstract:Abstract Studying the interaction between Serum Amyloid P comPonent (SAP) and β-Amyloid (Aβ) a new Aβ binding site was identified on the SAP near the known binding site at the two bound calcium ions. SAP stabilizes dePosits in neurodegenerative diseases, which is manifested via Aβ-binding. Because the inhibition of this interaction is a Potential theraPeutic target in neurodegeneration, the structural basis of SAP-Aβ binding was studied. The chymotryPtic digestion of SAP resulted in a 18,223 Da Product identified by mass sPectrometry. This cleavage was inhibited by Aβ revealing that this cleaving site between Tyr-140 and Gly-141 is involved in the interaction between SAP and Aβ⋅ These results suggest that the Aβ-binding site on SAP is larger than it was recently assumed.
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Glycosaminoglycans inhibit neurodegenerative effects of Serum Amyloid P comPonent in vitro.
Neurochemistry international, 2005Co-Authors: Zoltán Urbányi, Erika Forrai, Miklós Sárvári, István Likó, Janos Illes, Tamas PazmanyAbstract:Abstract Serum Amyloid P comPonent, a member of Pentraxin Serum Protein family, has been suggested to contribute to the Progression of neurodegeneration including Alzheimer's disease by binding to β-Amyloid fibrils leading to an increased stability of the dePosits against Proteolytic degradation and by inducing neuronal aPoPtosis. Here, we show that glycosaminoglycans inhibit both the Serum Amyloid P comPonent–β-Amyloid interaction and the neurotoxic effect of Serum Amyloid P comPonent. These effects correlate with the structure of glycosaminoglycans and show different structure–activity relationshiP in the case of the two different effects. While the efficacy of the inhibition on the Serum Amyloid P comPonent-induced cell death increases with the uronic acid content, the inhibitory activity on the Serum Amyloid P comPonent–β-Amyloid interaction decreases with the increasing uronic acid content of the glycosaminoglycans. The inhibitory effect of glycosaminoglycans on the interaction between the first comPonent of the comPlement cascade (C1q) and β-Amyloid shows a similar structure–activity relationshiP as on the Serum Amyloid P comPonent–β-Amyloid interaction. This suggests that glycosaminoglycans interfere with the binding site on β-Amyloid for Serum Amyloid P comPonent and C1q. The functional consequence of this binding has been demonstrated by heParin which Promotes the Proteolysis of β-Amyloid in vitro in the Presence of Serum Amyloid P comPonent. Our results suggest that glycosaminoglycans might have theraPeutical Potential on the neurodegeneration reducing its Progress.
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Serum Amyloid P comPonent induces neuronal aPoPtosis and beta-Amyloid immunoreactivity.
Brain research, 2003Co-Authors: Zoltán Urbányi, Miklós Sass, Lajos László, Thomas B Tomasi, Erzsébet Tóth, Eva Mekes, Tamas PazmanyAbstract:Previously we have rePorted Serum Amyloid P comPonent (SAP) induced cell death in cerebro-cortical cultures of rat brain. In this PaPer we studied the tyPes of target cells and the molecular mechanism of SAP-induced cell death. Immuno-electron and light microscoPy revealed that SAP Penetrates the Plasma membrane and translocates selectively into the nuclei of neurons. Neuronal cells with SAP immunoreactivity exhibit the morPhological hallmarks of aPoPtosis in vitro. The aPoPtotic mechanism of cell death is also suPPorted by the increased Bax/Bcl-2 ratio. In addition to neurotoxic effects, we detected elevated beta-Amyloid (Abeta) immunoreactivity following SAP treatment. This study suPPorts the thesis that SAP Plays an imPortant role in the Pathomechanism of neurodegenerative diseases, including Alzheimer's disease by inducing neuronal aPoPtosis.
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Serum Amyloid P comPonent induces neuronal aPoPtosis and β-Amyloid immunoreactivity
Brain Research, 2003Co-Authors: Zoltán Urbányi, Miklós Sass, Lajos László, Thomas B Tomasi, Erzsébet Tóth, Eva Mekes, Tamas PazmanyAbstract:Abstract Previously we have rePorted Serum Amyloid P comPonent (SAP) induced cell death in cerebro-cortical cultures of rat brain. In this PaPer we studied the tyPes of target cells and the molecular mechanism of SAP-induced cell death. Immuno-electron and light microscoPy revealed that SAP Penetrates the Plasma membrane and translocates selectively into the nuclei of neurons. Neuronal cells with SAP immunoreactivity exhibit the morPhological hallmarks of aPoPtosis in vitro. The aPoPtotic mechanism of cell death is also suPPorted by the increased Bax/Bcl-2 ratio. In addition to neurotoxic effects, we detected elevated β-Amyloid (Aβ) immunoreactivity following SAP treatment. This study suPPorts the thesis that SAP Plays an imPortant role in the Pathomechanism of neurodegenerative diseases, including Alzheimer’s disease by inducing neuronal aPoPtosis.
Dietger Stibenz - One of the best experts on this subject based on the ideXlab platform.
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Binding of human Serum Amyloid P comPonentto L-selectin
European Journal of Immunology, 2006Co-Authors: Dietger Stibenz, Michael Gräfe, Nils Debus, Michael Hasbach, Inke Bahr, Kristof Graf, Eckart Fleck, Usan Thanabalasingam, Christoph BührerAbstract:Serum concentrations of soluble L-selectin by far exceed those of other soluble adhesion molecules, and Serum soluble L-selectin concentrations are remarkably stable uPon Prolonged storage. We Present evidence for Ca2+-dePendent binding interactions between human Serum Amyloid P (SAP), a Proteolysis-resistant Pentraxin glycoProtein, and L-selectin, as shown by surface Plasmon resonance measurements, Protein band shift assays in a native PAGE system, and after SDS-PAGE and membrane transfer. Monoclonal antibodies to L-selectin strongly reduced binding of biotinylated SAP to L-selectin-IgG chimeras immobilized on microtiter Plates. As binding was reduced by Prior glycoPePtidase F treatment of L-selectin but not of SAP, it aPPears to be based on SAP lectin domain interactions with N-linked L-selectin carbohydrates. In freshly PrePared human lymPhocytes, SAP incubation induced exPression of a β2 integrin neoePitoPe associated with high-affinity binding. This was Partially blocked by Pre-incubation with Fab fragments of two anti-L-selectin antibodies. In flow chamber exPeriments, SAP inhibited the adherence of human neutroPhils to activated endothelium under shear stress. Thus, SAP binds to human L-selectin and affects L-selectin-dePendent leukocyte-endothelial interactions.
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Binding of human Serum Amyloid P comPonentto L‐selectin
European journal of immunology, 2006Co-Authors: Dietger Stibenz, Michael Gräfe, Nils Debus, Michael Hasbach, Inke Bahr, Kristof Graf, Eckart Fleck, Usan Thanabalasingam, Christoph BührerAbstract:Serum concentrations of soluble L-selectin by far exceed those of other soluble adhesion molecules, and Serum soluble L-selectin concentrations are remarkably stable uPon Prolonged storage. We Present evidence for Ca2+-dePendent binding interactions between human Serum Amyloid P (SAP), a Proteolysis-resistant Pentraxin glycoProtein, and L-selectin, as shown by surface Plasmon resonance measurements, Protein band shift assays in a native PAGE system, and after SDS-PAGE and membrane transfer. Monoclonal antibodies to L-selectin strongly reduced binding of biotinylated SAP to L-selectin-IgG chimeras immobilized on microtiter Plates. As binding was reduced by Prior glycoPePtidase F treatment of L-selectin but not of SAP, it aPPears to be based on SAP lectin domain interactions with N-linked L-selectin carbohydrates. In freshly PrePared human lymPhocytes, SAP incubation induced exPression of a β2 integrin neoePitoPe associated with high-affinity binding. This was Partially blocked by Pre-incubation with Fab fragments of two anti-L-selectin antibodies. In flow chamber exPeriments, SAP inhibited the adherence of human neutroPhils to activated endothelium under shear stress. Thus, SAP binds to human L-selectin and affects L-selectin-dePendent leukocyte-endothelial interactions.
M B Pepys - One of the best experts on this subject based on the ideXlab platform.
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Pharmacological removal of Serum Amyloid P comPonent from intracerebral Plaques and cerebrovascular Aβ Amyloid dePosits in vivo
2016Co-Authors: Al-shawi R, G A Tennent, Dj Millar, Richard-londt A, Brandner S, Dj Werring, Jp Simons, M B PepysAbstract:Human Amyloid dePosits always contain the normal Plasma Protein Serum Amyloid P comPonent (SAP), owing to its avid but reversible binding to all Amyloid fibrils, including the Amyloid β (Aβ) fibrils in the cerebral Parenchyma Plaques and cerebrovascular Amyloid dePosits of Alzheimer's disease (AD) and cerebral Amyloid angioPathy (CAA). SAP Promotes Amyloid fibril formation in vitro, contributes to Persistence of Amyloid in vivo and is also itself directly toxic to cerebral neurons. We therefore develoPed (R)-1-[6-[(R)-2-carboxy-Pyrrolidin-1-yl]-6-oxo-hexanoyl]Pyrrolidine-2-carboxylic acid (CPHPC), a drug that removes SAP from the blood, and thereby also from the cerebrosPinal fluid (CSF), in Patients with AD. Here we rePort that, after introduction of transgenic human SAP exPression in the TASTPM double transgenic mouse model of AD, all the Amyloid dePosits contained human SAP. DePletion of circulating human SAP by CPHPC administration in these mice removed all detectable human SAP from both the intracerebral and cerebrovascular Amyloid. The demonstration that removal of SAP from the blood and CSF also removes it from these Amyloid dePosits crucially validates the strategy of the forthcoming 'DePletion of Serum Amyloid P comPonent in Alzheimer's disease (DESPIAD)' clinical trial of CPHPC. The results also strongly suPPort clinical testing of CPHPC in Patients with CAA
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normal circulating Serum Amyloid P comPonent concentration in systemic sclerosis
Arthritis & Rheumatism, 2007Co-Authors: Glenys A. Tennent, Magdalena Dziadzio, Eva Triantafillidou, Phillip Davies, Ruth J Gallimore, Christopher P Denton, M B PepysAbstract:Objective: The observation of reduced circulating concentrations of the constitutive Plasma Pentraxin Protein, Serum Amyloid P comPonent (SAP), in Serum samPles obtained from a small number of Patients with systemic sclerosis (SSc) has been rePorted as confirmation of an antifibrotic role of this Protein. Because neither sustained SAP dePletion in humans nor SAP deficiency in mice is associated with fibrosis, we sought to establish rigorously the Serum SAP concentration in well-characterized Patients with SSc. Methods: Serum concentrations of SAP were measured by electroimmunoassay in a cross-sectional cohort of 20 Patients with diffuse cutaneous SSc and 12 Patients with limited cutaneous SSc, and in a seParate 12-month longitudinal cohort of 13 Patients with diffuse disease and 37 Patients with limited disease. The extent and severity of disease were characterized in detail at the time of Serum samPling. Serum concentrations of the classic acute-Phase reactants, C-reactive Protein and Serum Amyloid A Protein, were measured by immunonePhelometric assays. Results: SAP values were entirely within the normal range, regardless of the extent and severity of disease, aPart from a very few isolated raised values associated with acute intercurrent comPlications causing major acute-Phase resPonses. Conclusion: We observed no reduced circulating concentrations of SAP in Patients with SSc, nor any evidence of an association between SAP levels and the extent or severity of fibrosis.
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targeted Pharmacological dePletion of Serum Amyloid P comPonent for treatment of human Amyloidosis
Nature, 2002Co-Authors: M B Pepys, J Herbert, Laurence Lovat, Winston L Hutchinson, Glenys A. Tennent, Helen J Lachmann, J R Gallimore, Tamas Bartfai, Alexander AlanineAbstract:The normal Plasma Protein Serum Amyloid P comPonent (SAP) binds to fibrils in all tyPes of Amyloid dePosits, and contributes to the Pathogenesis of Amyloidosis. In order to intervene in this Process we have develoPed a drug, R-1-[6-[R-2-carboxy-Pyrrolidin-1-yl]-6-oxo-hexanoyl]Pyrrolidine-2-carboxylic acid, that is a comPetitive inhibitor of SAP binding to Amyloid fibrils. This Palindromic comPound also crosslinks and dimerizes SAP molecules, leading to their very raPid clearance by the liver, and thus Produces a marked dePletion of circulating human SAP. This mechanism of drug action Potently removes SAP from human Amyloid dePosits in the tissues and may Provide a new theraPeutic aPProach to both systemic Amyloidosis and diseases associated with local Amyloid, including Alzheimer's disease and tyPe 2 diabetes.
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ScintigraPhy with 123I-Serum Amyloid P comPonent in Alzheimer disease.
Alzheimer disease and associated disorders, 1998Co-Authors: Laurence Lovat, M B Pepys, A. A. J. O'brien, S. F. Armstrong, S Madhoo, Christopher J. Bulpitt, Martin N. Rossor, Philip N HawkinsAbstract:The neuroPathology of Alzheimer disease (AD) includes cerebral and cerebrovascular Amyloid dePosits comPosed of A beta Protein. Extracerebral dePosits of A beta, identified immunohistochemically, have also been rePorted but without evidence for the Presence of Amyloid fibrils. Serum Amyloid P comPonent (SAP) is a normal Plasma glycoProtein that binds to the fibrils in all tyPes of Amyloid dePosit, and radiolabeled SAP is a sPecific, sensitive, quantitative diagnostic tracer for systemic Amyloid dePosits in vivo. However, we rePort that in 11 Patients with Probable or definite AD, conventional whole body Planar scintigraPhy after injection of I-123-SAP revealed no detectable localization of tracer within the brain or elsewhere. Significant amounts of systemic extracerebral A beta Amyloid are thus Probably not a feature of AD. Also, although Plasma-derived SAP is always Present in the cerebral and cerebrovascular Amyloid lesions of AD, there was insufficient accumulation of injected labeled SAP to be detected by the Present routine methodology.
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imaging of haemodialysis associated Amyloidosis with 123i Serum Amyloid P comPonent
The Lancet, 1991Co-Authors: S R Nelson, Philip N Hawkins, D. Sethi, P. E. Gower, J.p. Lavender, S Richardson, Christopher W Pugh, Christopher G Winearls, D O Oliver, M B PepysAbstract:Long-term haemodialysis is frequently comPlicated by Amyloid dePosition in which the fibrils consist of beta 2-microglobulin. Dialysis-related Amyloid disease causes extensive morbidity and has been associated with deaths in some cases. All Amyloid dePosits contain Amyloid P comPonent that is derived from the normal circulating Protein, Serum Amyloid P comPonent (SAP). We have used scintigraPhic imaging after injection of 123I-labelled SAP to assess the distribution of Amyloidosis in 38 Patients receiving long-term haemodialysis for end-stage renal failure. There was focal localisation of tracer at all sites where histological examination confirmed Amyloid dePosition. SPlenic uPtake was seen in 12 Patients, indicating sPlenic Amyloidosis, but there was no evidence of other visceral involvement. 6 control subjects who had been dialysed for under 1.5 years showed no localisation of tracer, nor was there any uPtake of 123I-labelled human Serum albumin in 3 long-term dialysis Patients with histologically confirmed Amyloidosis and Positive 123I-SAP images. Negative scans were also obtained in 5 Patients who had been transPlanted 0.8-2.4 years Previously, desPite Past evidence of dialysis arthroPathy (5) and histologically Proven Amyloidosis (4). 123I-SAP scintigraPhy may be helPful as a non-invasive method for both the diagnosis and monitoring of dialysis-associated Amyloidosis.
