Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene
Abstract
The tissue amyloid deposits that characterize systemic amyloidosis, Alzheimer's disease and the transmissible spongiform encephalopathies always contain serum amyloid P component (SAP) bound to the amyloid fibrils. We have previously proposed that this normal plasma protein may contribute to amyloidogenesis by stabilizing the deposits. Here we show that the induction of reactive amyloidosis is retarded in mice with targeted deletion of the SAP gene. This first demonstration of the participation of SAP in pathogenesis of amyloidosis in vivo confirms that inhibition of SAP binding to amyloid fibrils is an attractive therapeutic target in a range of serious human diseases.
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The binding of SAP stabilizes amyloid fibrils and promotes their formation in the brain, thereby contributing to the pathogenesis of AD and cerebral amyloid angiopathy.
“The binding of SAP stabilizes amyloid fibrils85 and promotes their formation in the brain86,87, thereby contributing to the pathogenesis of AD and cerebral amyloid angiopathy88,89.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [88]
Cites
Amyloid P component. A critical review
Pepys, M. B., Booth, D. R., Hutchinson, W. L., Gallimore, J. R., Collins, I. M., & Hohenester, E. (1997) · Amyloid · doi:10.3109/13506129709003838 · Cited by 181 · see citing works
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Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self
Derbinski, J., Schulte, A., Kyewski, B., & Klein, L. (2001) · Nature Immunology · doi:10.1038/ni723 · Cited by 1,068 · see citing works
Garlanda, C., Bottazzi, B., Bastone, A., & Mantovani, A. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115756 · Cited by 885 · see citing works
An Integrated View of Humoral Innate Immunity: Pentraxins as a Paradigm
Bottazzi, B., Doni, A., Garlanda, C., & Mantovani, A. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101305 · Cited by 592 · see citing works
Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity
Bickerstaff, M., Botto, M., Hutchinson, W., Herbert, J., Tennent, G., Bybee, A., Mitchell, D., Cook, H., Butler, P., Walport, M., et al. (1999) · Nature Medicine · doi:10.1038/9544 · Cited by 548 · see citing works
“In support of this, mice lacking SAP through targeted deletion of the SAP gene were relatively resistant to induction of reactive systemic AA amyloi”
BackgroundSelf-citationTargeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
Pepys, M. B., Herbert, J., Hutchinson, W. L., Tennent, G. A., Lachmann, H. J., Gallimore, J. R., Lovat, L. B., Bartfai, T., Alanine, A., Hertel, C., et al. (2002) · Nature · doi:10.1038/417254a · Cited by 540 · see citing works
“Our recent finding that mice with targeted deletion of the SAP gene show retarded and reduced induction of experimental reactive systemic (AA type) amyloidosis confirmed that SAP does indeed contribute to pathogenesis of amyloidosi”
BackgroundSelf-citationIslet amyloid and type 2 diabetes mellitus.
Höppener, J., Bo, A.-R., & Lips, C. J. M. (2000) · New England Journal of Medicine · doi:10.1056/nejm200008103430607 · Cited by 499 · see citing works
Rambaran, R. N., & Serpell, L. C. (2008) · Prion · doi:10.4161/pri.2.3.7488 · Cited by 511 · see citing works
Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis
Yan, S. D., Zhu, H., Zhu, A., Golabek, A., Du, H., Roher, A., Yu, J., Soto, C., Schmidt, A. M., Stern, D., et al. (2000) · Nature Medicine · doi:10.1038/76216 · Cited by 343 · see citing works
Antibodies to human serum amyloid P component eliminate visceral amyloid deposits
Bodin, K., Ellmerich, S., Kahan, M., Tennent, G. A., Loesch, A., Gilbertson, J. A., Hutchinson, W. L., Mangione, P. P., Gallimore, J. R., Millar, D. J., et al. (2010) · Nature · doi:10.1038/nature09494 · Cited by 336 · see citing works
“We therefore investigated two of our mouse monoclonal IgG2a anti-SAP antibodies, designated SAP-5 and Abp1, which bound to human SAP with similar affinities, on rates and off rates (Supplementary 10), which activated mouse complement in vitro producing C3 cleavage comparable to that produced by the sheep polyclonal an…”
InfluentialSelf-citationMorozova-Roche, L., Zurdo, J., Spencer, A., Noppe, W., Receveur, V., Archer, D. B., Joniau, M., & Dobson, C. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4264 · Cited by 320 · see citing works
Islet amyloid and type 2 diabetes: from molecular misfolding to islet pathophysiology
Jaikaran, E. T. A. S., & Clark, A. (2001) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(01)00078-3 · Cited by 294 · see citing works
“Serum amyloid P component (SAP) is found in all amyloid deposits including islet amyloid [85] and has been proposed to protect amyloid from degradation rather than promote ¢brillogenesis [86].”
BackgroundAmyloids — a functional coat for microorganisms
Gebbink, M. F. B. G., Claessen, D., Bouma, B., Dijkhuizen, L., & Wösten, H. A. B. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1127 · Cited by 287 · see citing works
“, thereby contributing to the pathogenesis of amyloidosi”
Esposito, G., Michelutti, R., Verdone, G., Viglino, P., ÁNdez, H. H., Robinson, C. V., Amoresano, A., Dalpiaz, F., Monti, M., Pucci, P., et al. (2000) · Protein Science · doi:10.1110/ps.9.5.831 · Cited by 264 · see citing works
“…enzymes~Tennent et al., 1995!. DN6b2-m therefore might represent an ideal substrate for natural proteolytic enzymes following modification of the fibril by molecules capable of displacing SAP ~Botto et al., 1997! or inducing modifications of the fibril organization ~Merlini et al., 1995!.”
BackgroundAspects on human amyloid forms and their fibril polypeptides
Westermark, P. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.05024.x · Cited by 248 · see citing works
Pathogenesis, diagnosis and treatment of systemic amyloidosis.
Pepys, M. (2001) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.2000.0766 · Cited by 233 · see citing works
Self-citationMerlini, G., & Westermark, P. (2004) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.2003.01262.x · Cited by 219 · see citing works
Extracellular protein components of amyloid plaques and their roles in Alzheimer’s disease pathology
Rahman, M. M., & Lendel, C. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00465-0 · Cited by 245 · see citing works
Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?
Clark, A., & Nilsson, M. R. (2004) · Diabetologia · doi:10.1007/s00125-003-1304-4 · Cited by 186 · see citing works
“A proposal has been made that all amyloid deposits are being degraded continuously [110], possibly by removal by macrophages, and that accumulation of deposits could result from a deficiency in the factors responsible for degradation and/or turnover [111].”
BackgroundA protective role for innate immunity in systemic lupus erythematosus
Carroll, M. (2004) · Nature reviews. Immunology · doi:10.1038/nri1456 · Cited by 187 · see citing works
“fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=20219">SAP”
Klein, L., Klein, T. C., Rüther, U., & Kyewski, B. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.1.5 · Cited by 164 · see citing works
“Tolerance to a major murine APP has recently been documented (68).”
BackgroundExtracellular Chaperones and Proteostasis
Wyatt, A. R., Yerbury, J. J., Ecroyd, H. W., & Wilson, M. R. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-072711-163904 · Cited by 180 · see citing works
Amyloid P component. A critical review
Pepys, M. B., Booth, D. R., Hutchinson, W. L., Gallimore, J. R., Collins, I. M., & Hohenester, E. (1997) · Amyloid · doi:10.3109/13506129709003838 · Cited by 181 · see citing works
Self-citationLacombe, P., Mathews, P. M., Schmidt, S., Breidert, T., Heneka, M., Landreth, G., Feinstein, D. L., & Galea, E. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-11 · Cited by 179 · see citing works
“SAP is a non-fibrillar pentraxin plasma protein that contributes to amyloidosis by stabilizing amyloid fibrils, and is widely considered as a common component of amyloid deposits [46].”
Pentraxins in innate immunity: lessons from PTX3
Deban, L., Jaillon, S., Garlanda, C., Bottazzi, B., & Mantovani, A. (2010) · Cell and Tissue Research · doi:10.1007/s00441-010-1018-0 · Cited by 158 · see citing works
Rezk, T., & Hawkins, P. (2019) · Textbook of Autoinflammation · doi:10.1007/978-3-319-98605-0_15 · Cited by 173
Self-citationNoursadeghi, M., Bickerstaff, M., Gallimore, J., Herbert, J., Cohen, J., & Pepys, M. (2000) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.97.26.14584 · Cited by 162 · see citing works
Self-citationDoxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model
Cardoso, I., & Saraiva, M. (2006) · The FASEB Journal · doi:10.1096/fj.05-4509com · Cited by 161 · see citing works
“Furthermore, several reports indicate that although not essential in amyloid deposition, SAP significantly accelerates the reaction (26, 27 ).”
BackgroundDisrupting β-Amyloid Aggregation for Alzheimer Disease Treatment
Estrada, L. D., & Soto, C. A. (2006) · Current Topics in Medicinal Chemistry · doi:10.2174/156802607779318262 · Cited by 162 · see citing works
Pattern Recognition by Pentraxins
Agrawal, A., Singh, P. P., Bottazzi, B., Garlanda, C., & Mantovani, A. (2009) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4419-0901-5_7 · Cited by 153 · see citing works
Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis
Hawkins, P. (2002) · Current opinion in nephrology and hypertension · doi:10.1097/00041552-200211000-00013 · Cited by 147
Self-citationA Molecular History of the Amyloidoses
Buxbaum, J. N., & LINKE, R. P. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.01.024 · Cited by 151 · see citing works
Milde, R., Ritter, J. M., Tennent, G. A., Loesch, A., Martínez, F. O., Gordon, S., Pepys, M. B., Verschoor, A., & Helming, L. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.065 · Cited by 162 · see citing works
Self-citationWilson, M. R., Yerbury, J. J., & Poon, S. (2007) · Molecular BioSystems · doi:10.1039/b712728f · Cited by 142 · see citing works
“83; 84; 85 The interaction between SAP and amyloid fibrils is highly specific, and the abundance of SAP in amyloid fibrils relative to its trace concentration in plasma is extraordinary.(86) SAP has a protease-resistant pleated sheet structure that in the presence of Ca is resistant to proteolysis.”
Gillmore, J., Tennent, G., Hutchinson, W., Gallimore, J., Lachmann, H., Goodman, H., Offer, M., Millar, D., Petrie, A., Hawkins, P., et al. (2010) · British Journal of Haematology · doi:10.1111/j.1365-2141.2009.08036.x · Cited by 136
“Furthermore amyloid deposition is delayed and reduced in SAP knockout mice (Botto et al, 1997), confirming that SAP is a valid therapeutic target.”
BackgroundSelf-citationAmyloidosis and the respiratory tract
Gillmore, J., & Hawkins, P. (1999) · Thorax · doi:10.1136/thx.54.5.444 · Cited by 129
“The universal presence in amyloid of certain GAGs, notably heparan and dermatan sulphate, and SAP has long suggested that these moieties might contribute to its pathogenesis. The role of SAP has lately been confirmed in SAP “knock-out” mice in which experimentally induced AA amyloidosis was substantially reduced.”
BackgroundSelf-citationReview: Amyloidogenesis—Unquestioned Answers and Unanswered Questions
Kisilevsky, R. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4222 · Cited by 128 · see citing works
“The induction of AA amyloid has been examined in apoE and SAP knockout mice (Bales et al., 1997; Botto et al., 1997; Hoshii et al., 1997; Kindy and Rader, 1998; Elliot-Bryant and Cathcart, 1997).”
BackgroundBenson, M. (2003) · Baillière's Best Practice & Research : Clinical Rheumatology · doi:10.1016/j.berh.2003.09.001 · Cited by 120 · see citing works
Serum Amyloid P Aids Complement-Mediated Immunity to Streptococcus pneumoniae
Yuste, J., Botto, M., Bottoms, S., & Brown, J. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030120 · Cited by 117 · see citing works
“129(D1Mit105– 223) congenic mice were bred in-house by one of the authors (MB) [5,42].”
BackgroundMethodSelf-citationPathogenetic mechanisms of amyloid A amyloidosis
Simons, J., Al-Shawi, R., Ellmerich, S., Speck, I., Aslam, S., Hutchinson, W., Mangione, P., Disterer, P., Gilbertson, J., Hunt, T., et al. (2013) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1306621110 · Cited by 116
“-administered (125)I-human SAP ((125)I-hSAP), a validated, specific, quantitative in vivo tracer for systemic amyloid deposits in mice (14, 15) and humans (16–18).”
BackgroundMethodSelf-citationAndreasen, M., Lorenzen, N., & Otzen, D. E. (2015) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2015.01.018 · Cited by 106 · see citing works
Pentraxins: structure, function, and role in inflammation.
du Clos, T. W. (2013) · ISRN Inflammation · doi:10.1155/2013/379040 · Cited by 96 · see citing works
“In mice targeted deletion of the SAP gene leads to delayed amyloidogenesis in a reactive model of systemic amyloidosis [115].”
BackgroundHughes, M. M., Field, R. H., Perry, V. H., Murray, C. L., & Cunningham, C. (2010) · Glia · doi:10.1002/glia.21070 · Cited by 94 · see citing works
“In other amyloidoses macrophages are rather poor at removing amyloid by phagocytosis, extracellular proteolysis or other means and it has been shown that acute phase proteins such as serum amyloid protein and other pentraxins can coat amyloid proteins and prevent its phagocytosis (Botto et al., 1997; Tennent et al., 1…”
BackgroundThe Development of Serum Amyloid P as a Possible Therapeutic
Pilling, D., & Gomer, R. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02328 · Cited by 92 · see citing works
Tanigaki, K., Sacharidou, A., Peng, J.-Q., Chambliss, K., Yuhanna, I. S., Ghosh, D., Ahmed, M., Szalai, A., Vongpatanasin, W., Mattrey, R., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci89333 · Cited by 91 · see citing works
Self-citationWalker, L. C., & LeVine, H. (2000) · Molecular Neurobiology · doi:10.1385/mn:21:1-2:083 · Cited by 105 · see citing works
“Serum amyloid A deposition is delayed in mice deficient in serum amyloid P (83).”
BackgroundRydh, A., Suhr, O., Hietala, S., Åhlström, K. R., Pepys, M., & Hawkins, P. (1998) · European Journal of Nuclear Medicine · doi:10.1007/s002590050273 · Cited by 87
“The proportionate manner in which SAP binds to the fibrils has been demonstrated not only in vitro [15], but also in an animal experiment involving more than 500 mice [ 16 ] and in clinical autopsy studies [9, 17], all of which confirm remarkable quantitative concordance between labelled SAP uptake and amyloid histolo…”
Self-citationMulder, S. D., Nielsen, H. M., Blankenstein, M. A., Eikelenboom, P., & Veerhuis, R. (2014) · Glia · doi:10.1002/glia.22619 · Cited by 84 · see citing works
“, 1999), these AAPs also play an important role in the dynamic balance between Ab production and removal (Bales et al., 1997; Botto et al., 1997; DeMattos et al., 2002; Mucke et al., 2000), that may ultimately lead to amyloid plaque formation.”
BackgroundPersistent Lung Inflammation and Fibrosis in Serum Amyloid P Component (Apcs-/-) Knockout Mice
Pilling, D., & Gomer, R. H. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093730 · Cited by 77 · see citing works
“Naı̈ve Apcs mice have altered lung function Apcs mice were originally generated on a 129 background and then backcrossed to C57BL/6 mice [48,65].”
BackgroundMethodA Regulatory Role for Complement in Innate Immunity and Autoimmunity
Nauta, A., Roos, A., & Daha, M. (2004) · International Archives of Allergy and Immunology · doi:10.1159/000079261 · Cited by 80 · see citing works
“and participate in the pathogenesis of amyloidosis [”
BackgroundAmyloid precursors and amyloidosis in inflammatory arthritis.
Cunnane, G. (2001) · Current Opinion in Rheumatology · doi:10.1097/00002281-200101000-00011 · Cited by 80 · see citing works
Protein Aggregation and Fibrillogenesis in Cerebral and Systemic Amyloid Disease
Benseny‐Cases, N., Klementieva, O. L., & Cladera, J. (2012) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-5416-4 · Cited by 74 · see citing works
Heparan sulfate as a therapeutic target in amyloidogenesis: prospects and possible complications
Kisilevsky, R., Ancsin, J. B., Szarek, W. A., & Petanceska, S. S. (2007) · Amyloid · doi:10.1080/13506120601116419 · Cited by 79 · see citing works
Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component
Kolstoe, S., Ridha, B., Bellotti, V., Wang, N., Robinson, C., Crutch, S., Keir, G., Kukkastenvehmas, R., Gallimore, J., Hutchinson, W., et al. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0902640106 · Cited by 74 · see citing works
“SAP is highly resistant to proteolysis (10) and its binding stabilizes amyloid fibrils (11), enhances their formation in vitro (12), and contributes to their pathogenic deposition and/or persistence in vivo in systemic amyloidosis (13).”
BackgroundSelf-citationPinney, J., & Hawkins, P. N. (2012) · memo - Magazine of European Medical Oncology · doi:10.1007/s12254-012-0337-0 · Cited by 71
Self-citationGillmore, J., Hutchinson, W., Herbert, J., Bybee, A., Mitchell, D., Hasserjian, R., Yamamura, K., Suzuki, M., Sabin, C., & Pepys, M. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01860.x · Cited by 70 · see citing works
Self-citationRoles of Extracellular Chaperones in Amyloidosis
Wyatt, A. R., Yerbury, J. J., Dabbs, R. A., & Wilson, M. R. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.01.004 · Cited by 66 · see citing works
Inoue, S., Kuroiwa, M., Saraiva, M. J., Guimarães, A., & Kisilevsky, R. (1998) · Journal of Structural Biology · doi:10.1006/jsbi.1998.4052 · Cited by 67
The Pentraxins 1975–2018: Serendipity, Diagnostics and Drugs
Pepys, M. B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02382 · Cited by 67 · see citing works
“We then went on to create the first SAP knockout mice and to show that, although it was possible to induce systemic AA amyloidosis in them, it took longer than in wild type mice and the deposits were smaller (92).”
BackgroundSelf-citationHuman Serum Amyloid P Component is a Single Uncomplexed Pentamer in Whole Serum
Hutchinson, W. L., Hohenester, E., & Pepys, M. B. (2000) · Molecular Medicine · doi:10.1007/bf03401789 · Cited by 66 · see citing works
Self-citationInhibition of Amyloidosis Using Low-Molecular-Weight Heparins
Zhu, H., Yu, J., & Kindy, M. S. (2001) · Molecular Medicine · doi:10.1007/bf03401857 · Cited by 71 · see citing works
Novel Drugs Targeting Transthyretin Amyloidosis
Hanna, M. (2014) · Current Heart Failure Reports · doi:10.1007/s11897-013-0182-4 · Cited by 65 · see citing works
Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease
Nakagawa, N., Barron, L., Gomez, I. G., Johnson, B. G., Roach, A. M., Kameoka, S., Jack, R. M., Lupher, M. L., Gharib, S. A., & Duffield, J. S. (2016) · JCI Insight · doi:10.1172/jci.insight.87446 · Cited by 59 · see citing works
“(B) Glomerulosclerosis score ranged from none (0) to >75% of glomeruli affected (4).”
BackgroundDavies, K. T. J., Bennett, N. C., Tsagkogeorga, G., Rossiter, S. J., & Faulkes, C. G. (2015) · Molecular Biology and Evolution · doi:10.1093/molbev/msv175 · Cited by 63 · see citing works
“These genes included APCS which may play a role in Alzheimer's disease (Botto et al. 1997) play a role in obesity (He et al. 2001) and THRA, one of the receptors of thyroid hormone.”
Ochrietor, J., Harrison, K. A., Zahedi, K., & Mortensen, R. F. (2000) · Cytokine · doi:10.1006/cyto.2000.0668 · Cited by 60 · see citing works
de Haas, C. D., van der Tol, M. E., van Kessel, K. V., Verhoef, J., & van Strijp, J. V. (1998) · Journal of Immunology · doi:10.4049/jimmunol.161.7.3607 · Cited by 59 · see citing works
Utility of 18F-FDG PET(/CT) in patients with systemic and localized amyloidosis
Glaudemans, A., Slart, R., Noordzij, W., Dierckx, R., & Hazenberg, B. (2013) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-013-2375-1 · Cited by 58
The relation of proteoglycans, serum amyloid P and Apo E to amyloidosis current status, 2000
Kisilevsky, R. (2000) · Amyloid · doi:10.3109/13506120009146820 · Cited by 64 · see citing works
Emerging Therapeutics for the Treatment of Light Chain and Transthyretin Amyloidosis
Zhang, K. W., Stockerl-Goldstein, K. E., & Lenihan, D. J. (2019) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2019.02.002 · Cited by 61 · see citing works
“The pentraxins have also been found to promote amyloid deposition and disease progression in vivo (97).”
BackgroundMolecular chaperone properties of serum amyloid P component
Coker, A., Purvis, A., Baker, D., Pepys, M., & Wood, S. P. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01530-1 · Cited by 56 · see citing works
Self-citationGenes and susceptible loci of Alzheimer’s disease
Shastry, B. S., & Giblin, F. J. (1999) · Brain Research Bulletin · doi:10.1016/s0361-9230(98)00156-7 · Cited by 47 · see citing works
The long pentraxin PTX 3: A prototypical sensor of tissue injury and a regulator of homeostasis
Erreni, M., Manfredi, A. A., Garlanda, C., Mantovani, A., & Rovere, P. Q. (2017) · Immunological Reviews · doi:10.1111/imr.12570 · Cited by 60 · see citing works
Animal models of human amyloidoses: Are transgenic mice worth the time and trouble?
Buxbaum, J. N. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.07.031 · Cited by 53 · see citing works
“Thus, despite being present in the deposits of all forms of amyloid, SAP was not required for either fibril deposition or stability in vivo [23,24].”
BackgroundInnate immunity, hemostasis and matrix remodeling: PTX3 as a link
Doni, A., Garlanda, C., & Mantovani, A. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.10.012 · Cited by 53 · see citing works
“SAP has a role in amyloidosis where, through binding and consequent stabilization of amyloid fibrils, it promotes their persistence[105].”
BackgroundComplement C4 maintains peripheral B-cell tolerance in a myeloid cell-dependent manner
Chatterjee, P., Agyemang, A. F., Alimzhanov, M., Degn, S., Tsiftsoglou, S., Alicot, E., Jones, S. A., Ma, M.-H., & Carroll, M. (2013) · European Journal of Immunology · doi:10.1002/eji.201343412 · Cited by 52 · see citing works
An Insight into the Changes in Human Plasma Proteome on Adaptation to Hypobaric Hypoxia
Ahmad, Y., Sharma, N. K., Garg, I., Ahmad, M. F., Sharma, M., & Bhargava, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067548 · Cited by 54 · see citing works
“A contribution of SAP to amyloidogenesis in vivo has been conforrmed in SAP knockout mice [86].”
BackgroundAmyloidosis: new strategies for treatment.
Hirschfield, G., & Hawkins, P. (2003) · International Journal of Biochemistry and Cell Biology · doi:10.1016/s1357-2725(03)00169-9 · Cited by 51 · see citing works
Self-citationde Haas, C. D., van der Zee, R., Benaissa-Trouw, B., van Kessel, K. V., Verhoef, J., & van Strijp, J. V. (1999) · Infection and Immunity · doi:10.1128/iai.67.6.2790-2796.1999 · Cited by 51 · see citing works
“Reports about the involvement of SAP in the persistence of amyloid deposits are contradictory, demonstrating its contribution to amyloidosis by stabilizing the deposits (5, 13) but also showing its inhibition of the formation of Alzheimer b-peptide fibrils (24).”
BackgroundThe Sushi peptides: structural characterization and mode of action against Gram-negative bacteria
Ding, J., Li, P., & Ho, B. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-7456-0 · Cited by 50 · see citing works
Amyloid precursors and amyloidosis in rheumatoid arthritis.
Cunnane, G., & Whitehead, A. S. (1999) · Baillière's Best Practice & Research : Clinical Rheumatology · doi:10.1053/berh.1999.0049 · Cited by 48
Rutemark, C., Alicot, E., Bergman, A., Ma, M.-H., Getahun, A., Ellmerich, S., Carroll, M., & Heyman, B. (2011) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1109831108 · Cited by 47 · see citing works
“C1qA mice (57) were obtained from Marina Botto (Imperial College London, United Kingdom), and SAP (58) and CRP (59) mice were obtained from Mark Pepys (Imperial College London, United Kingdom).”
MethodInfluentialPathogenesis of β2‐microglobulin amyloidosis
Ohashi, K. (2001) · Pathology International · doi:10.1046/j.1440-1827.2001.01156.x · Cited by 59 · see citing works
New insights into the role of serum amyloid P component, a novel lipopolysaccharide-binding protein.
de Haas, C. D. (1999) · FEMS Immunology & Medical Microbiology · doi:10.1111/j.1574-695x.1999.tb01390.x · Cited by 46 · see citing works
“However, recently SAP knockout mice were produced that developed normally and were fertile, which suggests that despite the evolutionary conservation and presumably signi¢cant physiological function of SAP, blocking SAP binding in vivo may not have major adverse e¡ects [15].”
BackgroundSerum amyloid P component is an essential element of resistance against Aspergillus fumigatus
Doni, A., Parente, R., Laface, I., Magrini, E. I., Cunha, C., Colombo, F., de Lacerda, J. F., Campos, A., Mapelli, S. N., Petroni, F., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24021-y · Cited by 66 · see citing works
Self-citationApolipoprotein Serum Amyloid A in Alzheimer's Disease
Kindy, M., Yu, J., Guo, J.-T., & Zhu, H. (1999) · Journal of Alzheimer's Disease · doi:10.3233/jad-1999-1303 · Cited by 44 · see citing works
“The universal nature of amyloidoses and the importance of subcomponents associated with fibrillogenesis have been extensively studied [3,12,22,23,25,33,47,50,53,58].”
BackgroundSerum Amyloid P Component as a Biomarker in Mild Cognitive Impairment and Alzheimer’s Disease
Verwey, N., Schuitemaker, A., van der Flier, W. M., Mulder, S., Mulder, C., Hack, C., Scheltens, P., Blankenstein, M., & Veerhuis, R. (2008) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000178756 · Cited by 43 · see citing works
“SAP binds a variety of ligands, including As, in a Ca 2+ -dependent manner [ , ,”
BackgroundBi, B.-T., Lin, H.-B., Cheng, Y.-F., Zhou, H., Lin, T., Zhang, M.-Z., Li, T.-J., & Xu, J.-P. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2011.12.007 · Cited by 42 · see citing works
“SAP-deficient mice exhibited delayed amyloidosis development (Botto et al., 1997; Pepys et al., 1979).”
Amyloidosis Inhibition, a New Frontier of the Protein Corona
Chen, P.-Y., Ding, F., Cai, R., Javed, I., Yang, W., Zhang, Z., Li, Y., Davis, T., Ke, P.-C., & Chen, C.-Y. (2020) · Nano Today · doi:10.1016/j.nantod.2020.100937 · Cited by 41 · see citing works
Transthyretin Accelerates Vascular Aβ Deposition in a Mouse Model of Alzheimer's Disease
Wati, H., Kawarabayashi, T., Matsubara, E., Kasai, A., Hirasawa, T., Kubota, T., Harigaya, Y., Shoji, M., & Maeda, S. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00166.x · Cited by 36 · see citing works
“An amyloid-binding protein SAP protects amyloid fibrils from proteolysis in vitro (46), and the induction of AA amyloidosis is significantly retarded in the SAP-deficient mice relative to wild-type mice (4, 47).”
BackgroundSerum amyloid P colocalizes with apolipoproteins in human atheroma: functional implications
Stewart, C. R., Haw, A., Lopez, R., McDonald, T. O., Callaghan, J. M., McConville, M. J., Moore, K. J., Howlett, G. J., & O’Brien, K. D. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700098-jlr200 · Cited by 51 · see citing works
“A role for SAP as a regulator of amyloid fibril deposition is consistent with the observation that amyloid deposits form more slowly in mice lacking SAP than in wild-type mice when amyloid A amyloidosis is induced in response to chronic inflammation (46).”
BackgroundAmyloidosis: a clinico-pathophysiological synopsis.
Hirschfield, G. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2003.12.013 · Cited by 40
SAP: structure, function, and its roles in immune-related diseases.
Xi, D., Luo, T., Xiong, H., Liu, J., Lu, H., Li, M., Hou, Y., & Guo, Z.-G. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.03.179 · Cited by 39 · see citing works
Recent developments in targeting protein misfolding diseases
Denny, R. A., Gavrin, L. K., & Saiah, E. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.01.089 · Cited by 45 · see citing works
MacRaild, C. A., Stewart, C. R., Mok, Y.-F., Gunzburg, M. J., Perugini, M. A., Lawrence, L. J., Tirtaatmadja, V., Cooper-White, J. J., & Howlett, G. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314008200 · Cited by 49 · see citing works
Role of islet amyloid in type 2 diabetes mellitus: consequence or cause?
Höppener, J. W. M., Nieuwenhuis, M. G., Feltkamp‐Vroom, T. M., Åhrén, B., & Lips, C. J. M. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00266-6 · Cited by 36 · see citing works
Pepys, M., Gallimore, J., Lloyd, J., Li, Z., Graham, D., Taylor, G., Ellmerich, S., Mangione, P., Tennent, G., Hutchinson, W., et al. (2012) · JIM - Journal of Immunological Methods · doi:10.1016/j.jim.2012.07.013 · Cited by 38 · see citing works
Self-citationHeegaard, N. H. H. (1998) · Electrophoresis · doi:10.1002/elps.1150190314 · Cited by 38
Pinney, J., & Lachmann, H. (2012) · Sub-cellular biochemistry · doi:10.1007/978-94-007-5416-4_20 · Cited by 38
Reglődi, D., Jüngling, A., Longuespée, R., Kriegsmann, J., Casadonte, R., Kriegsmann, M., Juhász, T., Bardosi, S., Tamás, A., Fulop, B. D., et al. (2018) · The Journal of Pathology · doi:10.1002/path.5100 · Cited by 38 · see citing works
“both anti-amyloidogenic and pro-amyloidogenic effects have been described [65], its presence is usually attributed to its role in stabilizing the fibrils, thereby preventing proteolytic degradation [66,67].”
BackgroundDrug Insight: emerging therapies for amyloidosis
Gillmore, J. D., & Hawkins, P. N. (2006) · Nature Reviews Nephrology · doi:10.1038/ncpneph0169 · Cited by 40 · see citing works
Self-citationPepys, M. (2007) · Clinical medicine (London) · doi:10.7861/clinmedicine.7-6-562 · Cited by 35 · see citing works
Self-citation
- Authors
- Botto, M., Hawkins, P. N., Bickerstaff, M. C. M., Herbert, J., Bygrave, A. E., Mcbride, A., Hutchinson, W. L., Tennent, G. A., Walportz, M. J., & Pepys, M. B.
- Affiliations
- Hammersmith Hospital (GB)
- Venue
- Nature Medicine
- Published
- 1997-08
- Volume
- 3
- Issue
- 8
- Pages
- 855-859
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2035391976
- Cited by
- 266
- References
- 43
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 12 · 2014: 7 · 2013: 13 · 2012: 12
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- serum amyloid P component, amyloid deposition, AA amyloidosis, amyloid fibrils, amyloidogenesis, systemic amyloidosis, Alzheimer's disease, prion disease, therapeutic target
- MeSH terms
- Amyloid, Serum Amyloid P-Component, Amyloidosis, Animals, Caseins, Disease Models, Animal, Glycoproteins, Humans, Male, Mice, Inbred C57BL, Silver Nitrate, Gene Deletion, Mice
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