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Cited by 100Glycosylation and Glycoproteins ResearchNeuroinflammation and Neurodegeneration MechanismsPharmacological Receptor Mechanisms and Effects

Siglecs in Brain Function and Neurological Disorders

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Siddiqui, Shoib Sarwar, Matar, Rachel, Merheb, Maxime, Hodeify, Rawad, Vazhappilly, Cijo George, Marton, John, Shamsuddin, Syed Azharuddin, Al Zouabi, Hussain·2019·Cells
DOI 10.3390/cells8101125PMC PMC6829431
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Abstract

Siglecs (Sialic acid-binding immunoglobulin-type lectins) are a I-type lectin that typically binds sialic acid. Siglecs are predominantly expressed in immune cells and generate activating or inhibitory signals. They are also shown to be expressed on the surface of cells in the nervous system and have been shown to play central roles in neuroinflammation. There has been a plethora of reviews outlining the studies pertaining to Siglecs in immune cells. However, this review aims to compile the articles on the role of Siglecs in brain function and neurological disorders. In humans, the most abundant Siglecs are CD33 (Siglec-3), Siglec-4 (myelin-associated glycoprotein/MAG), and Siglec-11, Whereas in mice the most abundant are Siglec-1 (sialoadhesin), Siglec-2 (CD22), Siglec-E, Siglec-F, and Siglec-H. This review is divided into three parts. Firstly, we discuss the general biological aspects of Siglecs that are expressed in nervous tissue. Secondly, we discuss about the role of Siglecs in brain function and molecular mechanism for their function. Finally, we collate the available information on Siglecs and neurological disorders. It is intriguing to study this family of proteins in neurological disorders because they carry immunoinhibitory and immunoactivating motifs that can be vital in neuroinflammation.

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  • Several members of the SIGLEC protein family have been implicated for roles in neurodegenerative diseases, especially due to neuroinflammatory properties.

    “Regarding the MR findings of CD33 (SIGLEC‐3) in AD and SIGLEC‐9 in ALS, we note that several members of the SIGLEC protein family have been implicated for roles in neurodegenerative diseases, especially due to neuroinflammatory properties (Siddiqui et al, 2019).”

    From The genetic regulation of protein expression in cerebrospinal fluid (2023) · cites this paper as Siddiqui et al, 2019

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  1. [1]Freeze H.H. Eklund E.A. Ng B.G. Patterson M.C. Neurological Aspects of Human Glycosylation Disorders Annu. Rev. Neurosci. 2015 38 105 125 10.1146/annurev-neuro-071714-034019 25840006 PMC4809143 · DOI
  2. [2]Scott H. Panin V.M. N-Glycosylation in Regulation of the Nervous System Glycobiology of the Nervous System Yu R.K. Schengrund C.-L. Springer New York, NY, USA 2009 Volume 9 367 394 PMC4476505 25151388
  3. [3]Varki A. Schnaar R.L. Schauer R. Sialic Acids and Other Nonulosonic Acids Essentials of Glycobiology 3rd ed. Varki A. Cummings R.D. Esko J.D. Cold Spring Harbor Laboratory Press New York, NY, USA 2017
  4. [4]Schnaar R.L. Gerardy-Schahn R. Hildebrandt H. Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration Physiol. Rev. 2014 94 461 518 10.1152/physrev.00033.2013 24692354 PMC4044301 · DOI · Paper page
  5. [5]Pillai S. Netravali I.A. Cariappa A. Mattoo H. Siglecs and immune regulation Annu. Rev. Immunol. 2012 30 357 392 10.1146/annurev-immunol-020711-075018 22224769 PMC3781015 · DOI
  6. [6]Stamenkovic I. Seed B. The B-cell antigen CD22 mediates monocyte and erythrocyte adhesion Nature 1990 345 74 77 10.1038/345074a0 1691828 · DOI
  7. [7]Stamenkovic I. Sgroi D. Aruffo A. Sy M.S. Anderson T. The B lymphocyte adhesion molecule CD22 interacts with leukocyte common antigen CD45RO on T cells and α2-6 sialyltransferase, CD75, on B cells Cell 1991 66 1133 1144 10.1016/0092-8674(91)90036-X 1717156 · DOI
  8. [8]Crocker P. Kelm S. Dubois C. Martin B. McWilliam A. Shotton D. Paulson J. Gordon S. Purification and properties of sialoadhesin, a sialic acid-binding receptor of murine tissue macrophages EMBO J. 1991 10 1661 1669 10.1002/j.1460-2075.1991.tb07689.x 2050106 PMC452836 · DOI
  9. [9]Crocker P. Mucklow S. Bouckson V. McWilliam A. Willis A. Gordon S. Milon G. Kelm S. Bradfield P. Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains EMBO J. 1994 13 4490 4503 10.1002/j.1460-2075.1994.tb06771.x 7925291 PMC395382 · DOI
  10. [10]Kelm S. Pelz A. Schauer R. Filbin M.T. Tang S. De Bellard M.-E. Schnaar R.L. Mahoney J.A. Hartnell A. Bradfield P. Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily Curr. Boil. 1994 4 965 972 10.1016/S0960-9822(00)00220-7 7533044 · DOI
  11. [11]Crocker P.R. Clark E.A. Filbin M. Gordon S. Jones Y. Kehrl J.H. Kelm H. Douarin N.L. Powell L. Roder J. Siglecs: A family of sialic-acid binding lectins Glycobiology 2012 10.1093/glycob/8.1.0 9498912 · DOI · Paper page
  12. [12]Varki A. Angata T. Siglecs-The major subfamily of I-type lectins Glycobiology 2006 16 1R 27R 10.1093/glycob/cwj008 16014749 · DOI
  13. [13]Crocker P.R. Varki A. Siglecs, sialic acids and innate immunity Trends Immunol. 2001 22 337 342 10.1016/S1471-4906(01)01930-5 11377294 · DOI
  14. [14]Der Linden E.C.M.B.-V. Angata T. Reynolds S.A. Powell L.D. Hedrick S.M. Varki A. CD33/Siglec-3 Binding Specificity, Expression Pattern, and Consequences of Gene Deletion in Mice Mol. Cell. Boil. 2003 23 4199 4206 10.1128/MCB.23.12.4199-4206.2003 PMC156146 12773563 · DOI
  15. [15]Paulson J.C. Macauley M.S. Kawasaki N. Siglecs as sensors of self in innate and adaptive immune responses Ann. New York Acad. Sci. 2012 1253 37 48 10.1111/j.1749-6632.2011.06362.x 22288608 PMC3335958 · DOI
  16. [16]Angata T. Hayakawa T. Yamanaka M. Varki A. Nakamura M. Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates FASEB J. 2006 20 1964 1973 10.1096/fj.06-5800com 17012248 · DOI
  17. [17]Cao H. Lakner U. De Bono B. Traherne J.A. Trowsdale J. Barrow A.D. SIGLEC16encodes a DAP12-associated receptor expressed in macrophages that evolved from its inhibitory counterpartSIGLEC11and has functional and non-functional alleles in humans Eur. J. Immunol. 2008 38 2303 2315 10.1002/eji.200738078 18629938 · DOI
  18. [18]Kameda Y. Takahata M. Komatsu M. Mikuni S. Hatakeyama S. Shimizu T. Angata T. Kinjo M. Minami A. Iwasaki N. Siglec-15 Regulates Osteoclast Differentiation by Modulating RANKL-Induced Phosphatidylinositol 3-Kinase/Akt and Erk Pathways in Association With Signaling Adaptor DAP12 J. Bone Miner. Res. 2013 28 2463 2475 10.1002/jbmr.1989 23677868 · DOI
  19. [19]Takamiya R. Ohtsubo K. Takamatsu S. Taniguchi N. Angata T. The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway Glycobiology 2013 23 178 187 10.1093/glycob/cws139 23035012 · DOI
  20. [20]Ishida-Kitagawa N. Tanaka K. Bao X. Kimura T. Miura T. Kitaoka Y. Hayashi K. Sato M. Maruoka M. Ogawa T. Siglec-15 Protein Regulates Formation of Functional Osteoclasts in Concert with DNAX-activating Protein of 12 kDa (DAP12) J. Boil. Chem. 2012 287 17493 17502 10.1074/jbc.M111.324194 PMC3366812 22451653 · DOI
  21. [21]Ali S.R. Fong J.J. Carlin A.F. Busch T.D. Linden R. Angata T. Areschoug T. Parast M. Varki N. Murray J. Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B Streptococcus J. Exp. Med. 2014 211 1231 1242 10.1084/jem.20131853 24799499 PMC4042635 · DOI
  22. [22]Schwarz F. Landig C.S. Siddiqui S. Secundino I. Olson J. Varki N. Nizet V. Varki A. Paired Siglec receptors generate opposite inflammatory responses to a human-specific pathogen EMBO J. 2017 36 751 760 10.15252/embj.201695581 28100677 PMC5350563 · DOI
  23. [23]Stanczak M.A. Siddiqui S.S. Trefny M.P. Thommen D.S. Boligan K.F. Von Gunten S. Tzankov A. Tietze L. Lardinois D. Heinzelmann-Schwarz V. Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells J. Clin. Investig. 2018 128 4912 4923 10.1172/JCI120612 30130255 PMC6205408 · DOI
  24. [24]Brinkman-Van Der linden E.C.M. Hurtado-Ziola N. Hayakawa T. Wiggleton L. Benirschke K. Varki A. Varki N. Human-specific expression of Siglec-6 in the placenta Glycobiology 2007 17 922 931 10.1093/glycob/cwm065 17580316 · DOI · Paper page
  25. [25]Mitra N. Banda K. Altheide T.K. Schaffer L. Johnson-Pais T.L. Beuten J. Leach R.J. Angata T. Varki N. Varki A. SIGLEC12, a Human-specific Segregating (Pseudo)gene, Encodes a Signaling Molecule Expressed in Prostate Carcinomas J. Boil. Chem. 2011 286 23003 23011 10.1074/jbc.M111.244152 PMC3123068 21555517 · DOI
  26. [26]Dharmadhikari G. Stolz K. Hauke M. Morgan N.G. Varki A. De Koning E. Kelm S. Maedler K. Siglec-7 restores β-cell function and survival and reduces inflammation in pancreatic islets from patients with diabetes Sci. Rep. 2017 7 10.1038/srep45319 PMC5381285 28378743 · DOI
  27. [27]Estus S. Shaw B.C. Devanney N. Katsumata Y. Press E.E. Fardo D.W. Evaluation of CD33 as a genetic risk factor for Alzheimer’s disease Acta Neuropathol. 2019 138 187 199 10.1007/s00401-019-02000-4 30949760 PMC7035471 · DOI
  28. [28]Siew J.J. Chern Y. Microglial Lectins in Health and Neurological Diseases Front. Mol. Neurosci. 2018 11 10.3389/fnmol.2018.00158 PMC5960708 29867350 · DOI
  29. [29]Linnartz-Gerlach B. Mathews M. Neumann H. Sensing the neuronal glycocalyx by glial sialic acid binding immunoglobulin-like lectins Neuroscience 2014 275 113 124 10.1016/j.neuroscience.2014.05.061 24924144 · DOI · Paper page
  30. [30]Linnartz-Gerlach B. Kopatz J. Neumann H. Siglec functions of microglia Glycobiology 2014 24 794 799 10.1093/glycob/cwu044 24833613 · DOI
  31. [31]Landig C.S. Hazel A. Kellman B.P. Fong J.J. Schwarz F. Agarwal S. Varki N. Massari P. Lewis N.E. Ram S. Evolution of the exclusively human pathogen Neisseria gonorrhoeae: Human-specific engagement of immunoregulatory Siglecs Evol. Appl. 2019 12 337 349 10.1111/eva.12744 30697344 PMC6346652 · DOI
  32. [32]Tecle E. Reynoso H.S. Wang R. Gagneux P. The female reproductive tract contains multiple innate sialic acid-binding immunoglobulin-like lectins (Siglecs) that facilitate sperm survival J. Boil. Chem. 2019 294 11910 11919 10.1074/jbc.RA119.008729 PMC6682739 31201275 · DOI
  33. [33]Hartnell A. Steel J. Turley H. Jones M. Jackson D.G. Crocker P.R. Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations Blood 2001 97 288 296 10.1182/blood.V97.1.288 11133773 · DOI
  34. [34]Crocker P.R. Hartnell A. Munday J. Nath D. The potential role of sialoadhesin as a macrophage recognition molecule in health and disease Glycoconj. J. 1997 14 601 609 10.1023/A:1018588526788 9298693 · DOI
  35. [35]Jellusova J. Nitschke L. Regulation of B Cell Functions by the Sialic Acid-Binding Receptors Siglec-G and CD22 Front. Immunol. 2012 2 10.3389/fimmu.2011.00096 PMC3342095 22566885 · DOI
  36. [36]Andrews R.G. Torok-Storb B. Bernstein I.D. Myeloid-associated differentiation antigens on stem cells and their progeny identified by monoclonal antibodies Blood 1983 62 124 132 6190518
  37. [37]Freeman S.D. Kelm S. Barber E.K. Crocker P.R. Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules Blood 1995 85 2005 2012 7718872
  38. [38]Martínez-Esparza M. Miguel R.C.-S. Hernández-Caselles T. Pérez-Oliva A.B. Vicente-Fernández J.J. García-Peñarrubia P. Epitope mapping, expression and post-translational modifications of two isoforms of CD33 (CD33M and CD33m) on lymphoid and myeloid human cells Glycobiol. 2011 21 757 770 21278227
  39. [39]Hernández-Caselles T. Martínez-Esparza M. Pérez-Oliva A.B. Quintanilla-Cecconi A.M. García-Alonso A. Alvarez-López D.M.R. García-Peñarrubia P. A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: Two isoforms of CD33 are generated by alternative splicing J. Leukoc. Boil. 2006 79 46 58 10.1189/jlb.0205096 16380601 · DOI
  40. [40]Quarles R.H. Myelin sheaths: Glycoproteins involved in their formation, maintenance and degeneration Cell. Mol. Life Sci. 2002 59 1851 1871 10.1007/PL00012510 12530518 PMC11337757 · DOI
  41. [41]Quarles R.H. Everly J.L. Brady R.O. Evidence for the close association of a glycoprotein with myelin in rat brain J. Neurochem. 1973 21 1177 1191 10.1111/j.1471-4159.1973.tb07573.x 4761704 · DOI
  42. [42]Arquint M. Roder J. Chia L.S. Down J. Wilkinson D. Bayley H. Braun P. Dunn R. Molecular cloning and primary structure of myelin-associated glycoprotein Proc. Natl. Acad. Sci. USA 1987 84 600 604 10.1073/pnas.84.2.600 2432614 PMC304258 · DOI
  43. [43]Sutcliffe J. Milner R.J. Shinnick T.M. Bloom F.E. Identifying the protein products of brain-specific genes with antibodies to chemically synthesized peptides Cell 1983 33 671 682 10.1016/0092-8674(83)90010-7 6347394 · DOI
  44. [44]Vinson M. Strijbos P.J.L.M. Rowles A. Facci L. Moore S.E. Simmons D.L. Walsh F.S. Myelin-associated glycoprotein interacts with ganglioside GT1b. A mechanism for neurite outgrowth inhibition J. Boil. Chem. 2001 276 20280 20285 10.1074/jbc.M100345200 11279053 · DOI
  45. [45]Collins B.E. Yang L.J.-S. Mukhopadhyay G. Filbin M.T. Kiso M. Hasegawa A. Schnaar R.L. Sialic Acid Specificity of Myelin-associated Glycoprotein Binding J. Boil. Chem. 1997 272 1248 1255 10.1074/jbc.272.2.1248 8995428 · DOI
  46. [46]Trapp B.D. Myelin-Associated Glycoprotein Location and Potential Functions Ann. N. Y. Acad. Sci. 1990 605 29 43 10.1111/j.1749-6632.1990.tb42378.x 1702602 · DOI · Paper page
  47. [47]Angata T. Kerr S.C. Greaves D.R. Varki N.M. Crocker P.R. Varki A. Cloning and characterization of human Siglec-11: A recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia J. Biol. Chem. 2002 27 24466 24474 10.1074/jbc.M202833200 11986327 · DOI
  48. [48]Wang X. Mitra N. Cruz P. Deng L. Varki N. Angata T. Green E.D. Mullikin J. Hayakawa T. Varki A. Evolution of Siglec-11 and Siglec-16 Genes in Hominins Mol. Boil. Evol. 2012 29 2073 2086 10.1093/molbev/mss077 PMC3408085 22383531 · DOI
  49. [49]Hayakawa T. Angata T. Lewis A.L. Mikkelsen T.S. Varki N.M. Varki A. Evolution: A human-specific gene in microglia Science 2005 309 10.1126/science.1114321 16151003 · DOI
  50. [50]YU Z. MAOUI M. WU L. BANVILLE D. SHEN S.-H. mSiglec-E, a novel mouse CD33-related siglec (sialic acid-binding immunoglobulin-like lectin) that recruits Src homology 2 (SH2)-domain-containing protein tyrosine phosphatases SHP-1 and SHP-2 Biochem. J. 2015 353 483 492 10.1042/bj3530483 PMC1221593 11171044 · DOI
  51. [51]Siddiqui S. Schwarz F. Springer S. Khedri Z. Yu H. Deng L. Verhagen A. Naito-Matsui Y. Jiang W. Kim D. Studies on the detection, expression, glycosylation, dimerization, and ligand binding properties of mouse Siglec-E J. Biol. Chem. 2017 292 1029 1037 10.1074/jbc.M116.738351 27920204 PMC5247637 · DOI
  52. [52]Zhang J.Q. Biedermann B. Nitschke L. Crocker P.R. The murine inhibitory receptor mSiglec-E is expressed broadly on cells of the innate immune system whereas mSiglec-F is restricted to eosinophils Eur. J. Immunol. 2004 34 1175 1184 10.1002/eji.200324723 15048729 · DOI
  53. [53]Uchiyama S. Sun J. Fukahori K. Ando N. Wu M. Schwarz F. Siddiqui S.S. Varki A. Marth J.D. Nizet V. Dual actions of group B Streptococcus capsular sialic acid provide resistance to platelet-mediated antimicrobial killing Proc. Natl. Acad. Sci. USA 2019 116 7465 7470 10.1073/pnas.1815572116 30910970 PMC6462088 · DOI
  54. [54]Spence S. Greene M.K. Fay F. Hams E. Saunders S.P. Hamid U. Fitzgerald M. Beck J. Bains B.K. Smyth P. Targeting Siglecs with a sialic acid-decorated nanoparticle abrogates inflammation Sci. Transl. Med. 2015 7 ra140 10.1126/scitranslmed.aab3459 26333936 · DOI
  55. [55]Läubli H. Pearce O.M.T. Schwarz F. Siddiqui S.S. Deng L. Stanczak M.A. Deng L. Verhagen A. Secrest P. Lusk C. Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer Proc. Natl. Acad. Sci. USA 2014 111 14211 14216 10.1073/pnas.1409580111 25225409 PMC4191788 · DOI
  56. [56]Boyd C.R. Orr S.J. Spence S. Burrows J.F. Elliott J. Carroll H.P. Brennan K. Ni Gabhann J. Coulter W.A. Johnston J.A. Siglec-E is up-regulated and phosphorylated following lipopolysaccharide stimulation in order to limit TLR-driven cytokine production J. Immunol. 2010 183 7703 7709 10.4049/jimmunol.0902780 PMC5580793 19933851 · DOI
  57. [57]Chen G.-Y. Brown N.K. Wu W. Khedri Z. Yu H. Chen X. van de Vlekkert D. D’Azzo A. Zheng P. Liu Y. Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1 Elife 2014 3 10.7554/eLife.04066 PMC4168287 25187624 · DOI
  58. [58]McMillan S.J. Sharma R.S. McKenzie E.J. Richards H.E. Zhang J. Prescott A. Crocker P.R. Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b b2-integrin-dependent signaling Blood 2013 121 2084 2094 10.1182/blood-2012-08-449983 23315163 PMC3596968 · DOI
  59. [59]Schwarz F. Pearce O.M. Wang X. Samraj A.N. Läubli H. Garcia J.O. Lin H. Fu X. Garcia-Bingman A. Secrest P. Siglec receptors impact mammalian lifespan by modulating oxidative stress Elife 2015 4 10.7554/eLife.06184 PMC4384638 25846707 · DOI
  60. [61]Angata T. Cloning and Characterization of a Novel Mouse Siglec, mSiglec-F. DIFFERENTIAL EVOLUTION OF THE MOUSE AND HUMAN (CD33) Siglec-3-RELATED GENE CLUSTERS J. Boil. Chem. 2001 276 45128 45136 10.1074/jbc.M108573200 11579105 · DOI
  61. [62]Tateno H. Crocker P.R. Paulson J.C. Mouse Siglec-F and human Siglec-8 are functionally convergent paralogs that are selectively expressed on eosinophils and recognize 6′-sulfo-sialyl Lewis X as a preferred glycan ligand Glycobiology 2005 15 1125 1135 10.1093/glycob/cwi097 15972893 · DOI
  62. [63]Wielgat P. Braszko J.J. The participation of sialic acids in microglia–neuron interactions Cell. Immunol. 2012 273 17 22 10.1016/j.cellimm.2011.12.002 22209424 · DOI
  63. [64]Blasius A.L. Colonna M. Sampling and signaling in plasmacytoid dendritic cells: The potential roles of Siglec-H Trends Immunol. 2006 27 255 260 10.1016/j.it.2006.04.005 16679063 · DOI
  64. [65]Konishi H. Kobayashi M. Kunisawa T. Imai K. Sayo A. Malissen B. Crocker P.R. Sato K. Kiyama H. Siglec-H is a microglia-specific marker that discriminates microglia from CNS-associated macrophages and CNS-infiltrating monocytes Glia 2017 65 1927 1943 10.1002/glia.23204 28836308 · DOI
  65. [66]Perry V.H. Crocker P.R. Gordon S. The blood–brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia J. Cell Sci. 1992 101 201 207 1569124
  66. [67]Mott R.T. Ait-Ghezala G. Town T. Mori T. Vendrame M. Zeng J. Ehrhart J. Mullan M. Tan J. Mullan M. Neuronal expression of CD22: Novel mechanism for inhibiting microglial proinflammatory cytokine production Glia 2004 46 369 379 10.1002/glia.20009 15095367 · DOI
  67. [69]Johnson P.W. Abramow-Newerly W. Seilheimer B. Sadoul R. Tropak M.B. Arquint M. Dunn R.J. Schachner M. Roder J.C. Recombinant myelin-associated glycoprotein confers neural adhesion and neurite outgrowth function Neuron 1989 3 377 385 10.1016/0896-6273(89)90262-6 2484339 · DOI
  68. [70]Turnley A.M. Bartlett P.F. MAG and MOG enhance neurite outgrowth of embryonic mouse spinal cord neurons NeuroReport 1998 9 1987 1990 10.1097/00001756-199806220-00013 9674579 · DOI
  69. [71]Mukhopadhyay G. Doherty P. Walsh F.S. Crocker P.R. Filbin M.T. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration Neuron 1994 13 757 767 10.1016/0896-6273(94)90042-6 7522484 · DOI
  70. [72]Quarles R.H. Myelin-associated glycoprotein (MAG): Past, present and beyond J. Neurochem. 2007 100 1431 1448 10.1111/j.1471-4159.2006.04319.x 17241126 · DOI
  71. [73]Cai D. Qiu J. Cao Z. McAtee M. Bregman B.S. Filbin M.T. Neuronal Cyclic AMP Controls the Developmental Loss in Ability of Axons to Regenerate J. Neurosci. 2001 21 4731 4739 10.1523/JNEUROSCI.21-13-04731.2001 11425900 PMC6762375 · DOI
  72. [74]McKerracher L. Rosen K.M. MAG, myelin and overcoming growth inhibition in the CNS Front. Mol. Neurosci. 2015 8 10.3389/fnmol.2015.00051 26441514 PMC4561339 · DOI
  73. [75]Bartsch U. Bandtlow C.E. Schnell L. Bartsch S. Spillmann A.A. Rubin B.P. Hillenbrand R. Schwab D.M.E. Schachner M. Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS Neuron 1995 15 1375 1381 10.1016/0896-6273(95)90015-2 8845160 · DOI
  74. [76]Tang S. Woodhall R.W. Shen Y.J. Debellard M.E. Saffell J.L. Doherty P. Walsh F.S. Filbin M.T. Soluble myelin-associated glycoprotein (MAG) found in vivo inhibits axonal regeneration Mol. Cell. Neurosci. 1997 9 333 346 10.1006/mcne.1997.0633 9361272 · DOI
  75. [77]Tang S. Qiu J. Nikulina E. Filbin M.T. Soluble Myelin-Associated Glycoprotein Released from Damaged White Matter Inhibits Axonal Regeneration Mol. Cell. Neurosci. 2001 18 259 269 10.1006/mcne.2001.1020 11591127 · DOI
  76. [78]Linnartz B. Wang Y. Neumann H. Microglial Immunoreceptor Tyrosine-Based Activation and Inhibition Motif Signaling in Neuroinflammation Int. J. Alzheimer’s Dis. 2010 2010 1 7 10.4061/2010/587463 PMC2915791 20721346 · DOI · Paper page
  77. [79]Wang Y. Neumann H. Alleviation of Neurotoxicity by Microglial Human Siglec-11 J. Neurosci. 2010 30 3482 3488 10.1523/JNEUROSCI.3940-09.2010 20203208 PMC6634112 · DOI
  78. [80]Pshezhetsky A.V. Ashmarina M. Keeping it trim: Roles of neuraminidases in CNS function Glycoconj. J. 2018 35 375 386 10.1007/s10719-018-9837-4 30088207 PMC6182584 · DOI
  79. [81]Kopatz J. Beutner C. Welle K. Bodea L.-G. Reinhardt J. Claude J. Linnartz-Gerlach B. Neumann H. Linnartz-Gerlach B. Siglec-h on activated microglia for recognition and engulfment of glioma cells Glia 2013 61 1122 1133 10.1002/glia.22501 23633299 · DOI
  80. [82]Groh J. Ribechini E. Stadler D. Schilling T. Lutz M.B. Martini R. Sialoadhesin promotes neuroinflammation-related disease progression in two mouse models of CLN disease Glia 2016 64 792 809 10.1002/glia.22962 26775238 · DOI
  81. [83]Mabbott N. How do PrPSc Prions Spread between Host Species, and within Hosts? Pathogens 2017 6 60 10.3390/pathogens6040060 PMC5750584 29186791 · DOI
  82. [84]Bradford B.M. Crocker P.R. Mabbott N.A. Peripheral prion disease pathogenesis is unaltered in the absence of sialoadhesin (Siglec-1/CD169) Immunology 2014 143 120 129 10.1111/imm.12294 24684244 PMC4137961 · DOI
  83. [85]Ip C.W. Kroner A. Crocker P.R. Nave K.-A. Martini R. Sialoadhesin deficiency ameliorates myelin degeneration and axonopathic changes in the CNS of PLP overexpressing mice Neurobiol. Dis. 2007 25 105 111 10.1016/j.nbd.2006.08.023 17064921 · DOI
  84. [86]Bertram L. Lange C. Mullin K. Parkinson M. Hsiao M. Hogan M.F. Schjeide B.M.M. Hooli B. DiVito J. Ionita I. Genome-wide Association Analysis Reveals Putative Alzheimer’s Disease Susceptibility Loci in Addition to APOE Am. J. Hum. Genet. 2008 83 623 10.1016/j.ajhg.2008.10.008 18976728 PMC2668052 · DOI · Paper page
  85. [87]Hollingworth P. Harold D. Sims R. Gerrish A. Lambert J.C. Carrasquillo M.M. Abraham R. Hamshere M.L. Pahwa J.S. Moskvina V. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease Nat. Genet. 2011 43 429 435 10.1038/ng.803 21460840 PMC3084173 · DOI · Paper page
  86. [88]Walker D.G. Whetzel A.M. Serrano G. Sue L.I. Beach T.G. Lue L.F. Association of CD33 polymorphism rs3865444 with Alzheimer’s disease pathology and CD33 expression in human cerebral cortex Neurobiol. Aging 2015 36 571 582 10.1016/j.neurobiolaging.2014.09.023 25448602 PMC4315751 · DOI · Paper page
  87. [90]Griciuc A. Serrano-Pozo A. Parrado A.R. Lesinski A.N. Asselin C.N. Mullin K. Hooli B. Choi S.H. Hyman B.T. Tanzi R.E. Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta Neuron 2013 78 631 643 10.1016/j.neuron.2013.04.014 23623698 PMC3706457 · DOI · Paper page
  88. [91]Malik M. Simpson J.F. Parikh I. Wilfred B.R. Fardo D.W. Nelson P.T. Estus S. CD33 Alzheimer’s Risk-Altering Polymorphism, CD33 Expression, and Exon 2 Splicing J. Neurosci. 2013 33 13320 13325 10.1523/JNEUROSCI.1224-13.2013 23946390 PMC3742922 · DOI · Paper page
  89. [94]Siddiqui S.S. Springer S.A. Verhagen A. Sundaramurthy V. Alisson-Silva F. Jiang W. Ghosh P. Varki A. The Alzheimer’s Disease–protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool J. Biol. Chem. 2017 292 15312 15320 10.1074/jbc.M117.799346 28747436 PMC5602391 · DOI
  90. [95]Fruttiger M. Montag D. Schachner M. Martini R. Crucial Role for the Myelin-associated Glycoprotein in the Maintenance of Axon-Myelin Integrity Eur. J. Neurosci. 1995 7 511 515 10.1111/j.1460-9568.1995.tb00347.x 7539694 · DOI
  91. [96]Bjartmar C. Trapp B.D. Axonal and neuronal degeneration in multiple sclerosis: Mechanisms and functional consequences Curr. Opin. Neurol. 2001 14 271 278 10.1097/00019052-200106000-00003 11371748 · DOI
  92. [97]Barbay S. Plautz E.J. Zoubina E. Frost S.B. Cramer S.C. Nudo R.J. Effects of Postinfarct Myelin-Associated Glycoprotein Antibody Treatment on Motor Recovery and Motor Map Plasticity in Squirrel Monkeys Stroke 2015 46 1620 1625 10.1161/STROKEAHA.114.008088 25931462 · DOI
  93. [98]Dalakas M.C. Advances in the diagnosis, immunopathogenesis and therapies of IgM-anti-MAG antibody-mediated neuropathies Ther. Adv. Neurol. Disord. 2018 11 10.1177/1756285617746640 PMC5791554 29403542 · DOI
  94. [99]Ilyas A.A. Quarles R.H. MacIntosh T.D. Dobersen M.J. Trapp B.D. Dalakas M.C. Brady R.O. IgM in a human neuropathy related to paraproteinemia binds to a carbohydrate determinant in the myelin-associated glycoprotein and to a ganglioside Proc. Natl. Acad. Sci. USA 1984 81 1225 1229 10.1073/pnas.81.4.1225 6199795 PMC344799 · DOI
  95. [100]Dalakas M.C. Pathogenesis and Treatment of Anti-MAG Neuropathy Curr. Treat. Options Neurol. 2010 12 71 83 10.1007/s11940-010-0065-x 20842571 · DOI
  96. [101]Brennaman L.H. Maness P.F. NCAM in Neuropsychiatric and Neurodegenerative Disorders Structure and Function of the Neural Cell Adhesion Molecule NCAM Berezin V. Springer New York, NY, USA 2009
  97. [102]Vawter M.P. Dysregulation of the neural cell adhesion molecule and neuropsychiatric disorders Eur. J. Pharmacol. 2000 405 385 395 10.1016/S0014-2999(00)00568-9 11033343 · DOI
  98. [103]Pham M.T. Pollock K.M. Rose M.D. Cary W.A. Stewart H.R. Zhou P. Nolta J.A. Waldau B. Generation of human vascularized brain organoids NeuroReport 2018 29 588 593 10.1097/WNR.0000000000001014 29570159 PMC6476536 · DOI
  99. [104]Oetke C. Vinson M.C. Jones C. Crocker P.R. Sialoadhesin-Deficient Mice Exhibit Subtle Changes in B- and T-Cell Populations and Reduced Immunoglobulin M Levels Mol. Cell. Boil. 2006 26 1549 1557 10.1128/MCB.26.4.1549-1557.2006 PMC1367192 16449664 · DOI
  100. [105]Nitschke L. Carsetti R. Ocker B. Köhler G. Lamers M.C. CD22 is a negative regulator of B-cell receptor signalling Curr. Boil. 1997 7 133 143 10.1016/S0960-9822(06)00057-1 9016707 · DOI
  101. [106]Samardzic T. Marinkovic D. Danzer C.P. Gerlach J. Nitschke L. Wirth T. Reduction of marginal zone B cells in CD22-deficient mice Eur. J. Immunol. 2002 32 561 567 10.1002/1521-4141(200202)32:2<561::AID-IMMU561>3.0.CO;2-H 11828373 · DOI
  102. [107]Li M. Shibata A. Li C. Braun P.E. McKerracher L. Roder J. Kater S.B. David S. Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse J. Neurosci. Res. 1996 46 404 414 10.1002/(SICI)1097-4547(19961115)46:4<404::AID-JNR2>3.0.CO;2-K 8950700 · DOI
  103. [108]DeBellard M.-E. Tang S. Mukhopadhyay G. Shen Y.-J. Filbin M.T. Myelin-Associated Glycoprotein Inhibits Axonal Regeneration from a Variety of Neurons via Interaction with a Sialoglycoprotein Mol. Cell. Neurosci. 1996 7 89 101 10.1006/mcne.1996.0007 8731478 · DOI
  104. [109]Montag D. Giese K.P. Bartsch U. Martini R. Lang Y. Blüthmann H. Karthigasan J. Kirschner D.A. Wintergerst E.S. Nave K.-A. Mice deficient for the glycoprotein show subtle abnormalities in myelin Neuron 1994 13 229 246 10.1016/0896-6273(94)90472-3 7519026 · DOI
  105. [110]Karlstetter M. Kopatz J. Aslanidis A. Shahraz A. Caramoy A. Linnartz-Gerlach B. Lin Y. Lückoff A. Fauser S. Düker K. Polysialic acid blocks mononuclear phagocyte reactivity, inhibits complement activation, and protects from vascular damage in the retina EMBO Mol. Med. 2017 9 154 166 10.15252/emmm.201606627 28003336 PMC5286381 · DOI
  106. [111]Zhang M. Angata T. Cho J.Y. Miller M. Broide D.H. Varki A. Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils Blood 2007 109 4280 4287 10.1182/blood-2006-08-039255 17272508 PMC1885492 · DOI
  107. [112]McMillan S.J. Richards H.E. Crocker P.R. Siglec-F-dependent negative regulation of allergen-induced eosinophilia depends critically on the experimental model Immunol. Lett. 2014 160 11 16 10.1016/j.imlet.2014.03.008 24698729 PMC4045373 · DOI
  108. [113]Schmitt H. Sell S. Koch J. Seefried M. Sonnewald S. Daniel C. Winkler T.H. Nitschke L. Siglec-H protects from virus-triggered severe systemic autoimmunity J. Exp. Med. 2016 213 1627 1644 10.1084/jem.20160189 27377589 PMC4986536 · DOI

Cited by

Sorted by citations

Authors
Siddiqui, S. S., Matar, R., Merheb, M., Hodeify, R., Vazhappilly, C. G., Marton, J., Shamsuddin, S. A., & Al Zouabi, H.
Affiliations
  • American University of Ras Al Khaimah (AE)
  • Department of Biotechnology, American University of Ras Al Khaimah (AURAK), Ras Al Khaimah 10021, UAE
Corresponding author
Siddiqui, Shoib Sarwar
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2019-09-22
Volume
8
Issue
10
Pages
1125
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells8101125
PMC
PMC6829431
OpenAlex
W2974166216
Cited by
100
References
5
Citations by year
2026: 8 · 2025: 11 · 2024: 28 · 2023: 12 · 2022: 18 · 2021: 13 · 2020: 10
FWCI
0.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
American University of Ras Al Khaimah (AURAK) (AAS/003/19)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
Keywords
Siglecs, brain function, neurological disorders, neuroinflammation, CD33, myelin-associated glycoprotein, sialoadhesin, CD22, Siglec-E, Siglec-F, nervous system
MeSH terms
Animals, Brain, Humans, Nervous System Diseases, Antigens, CD, Myelin-Associated Glycoprotein, N-Acetylneuraminic Acid, Mice, Sialic Acid Binding Ig-like Lectin 2, Sialic Acid Binding Immunoglobulin-like Lectins, Sialic Acid Binding Ig-like Lectin 3

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