Genomes and Genes
myelin associated glycoprotein
Summary: A myelin protein found in the periaxonal membrane of both the central and peripheral nervous systems myelin sheaths. It binds to cells surface receptors found on AXONS and may regulate cellular interactions between MYELIN and AXONS.
- Delarasse C, Della Gaspera B, Lu C, Lachapelle F, Gelot A, Rodriguez D, et al. Complex alternative splicing of the myelin oligodendrocyte glycoprotein gene is unique to human and non-human primates. J Neurochem. 2006;98:1707-17 pubmed publisher..These findings are discussed within the framework of a biological basis for phenotype diversity in recent mammalian evolution and for the notoriously variable clinical expression of diseases such as multiple sclerosis...
- Quarles R. Myelin-associated glycoprotein (MAG): past, present and beyond. J Neurochem. 2007;100:1431-48 pubmed
- Krishnamoorthy G, Lassmann H, Wekerle H, Holz A. Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation. J Clin Invest. 2006;116:2385-92 pubmed..In addition, in OSE mice, but not in single-transgenic parental mice, anti-MOG antibodies were switched from IgM to IgG1. ..
- O Connor K, McLaughlin K, De Jager P, Chitnis T, Bettelli E, Xu C, et al. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med. 2007;13:211-7 pubmed..MOG-specific autoantibodies were identified in a subset of ADEM but only rarely in adult-onset MS cases, indicating that MOG is a more prominent target antigen in ADEM than MS. ..
- Cao Z, Qiu J, Domeniconi M, Hou J, Bryson J, Mellado W, et al. The inhibition site on myelin-associated glycoprotein is within Ig-domain 5 and is distinct from the sialic acid binding site. J Neurosci. 2007;27:9146-54 pubmed..We conclude that the inhibition site on MAG is carried by Ig domain 5 and that this site is distinct from the sialic-acid binding site. ..
- Marta M, Andersson A, Isaksson M, Kämpe O, Lobell A. Unexpected regulatory roles of TLR4 and TLR9 in experimental autoimmune encephalomyelitis. Eur J Immunol. 2008;38:565-75 pubmed publisher..Importantly, we demonstrate that TLR4 and TLR9 regulate disease severity in MOG-induced EAE. ..
- Marta C, Oliver A, Sweet R, Pfeiffer S, Ruddle N. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology. Proc Natl Acad Sci U S A. 2005;102:13992-7 pubmed
- Park J, Yiu G, Kaneko S, Wang J, Chang J, He X, et al. A TNF receptor family member, TROY, is a coreceptor with Nogo receptor in mediating the inhibitory activity of myelin inhibitors. Neuron. 2005;45:345-51 pubmed..Our results implicate TROY in mediating myelin inhibition, offering new insights into the molecular mechanisms of regeneration failure in the adult nervous system. ..
- Shao Z, Browning J, Lee X, Scott M, Shulga Morskaya S, Allaire N, et al. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron. 2005;45:353-9 pubmed..Given the limited expression of p75, the discovery of TAJ function is an important step for understanding the regulation of axonal regeneration. ..
- Weaver A, Goncalves da Silva A, Nuttall R, Edwards D, Shapiro S, Rivest S, et al. An elevated matrix metalloproteinase (MMP) in an animal model of multiple sclerosis is protective by affecting Th1/Th2 polarization. FASEB J. 2005;19:1668-70 pubmed..These results emphasize that specific MMPs can have beneficial roles in inflammation, and they implicate MMPs in T effector polarization for the first time. ..
- Erb M, Flueck B, Kern F, Erne B, Steck A, Schaeren Wiemers N. Unraveling the differential expression of the two isoforms of myelin-associated glycoprotein in a mouse expressing GFP-tagged S-MAG specifically regulated and targeted into the different myelin compartments. Mol Cell Neurosci. 2006;31:613-27 pubmed..In summary, our data provide new insight in the subcellular distribution of the two isoforms fundamental for the understanding of their specific functions in myelin formation and maintenance. ..
- Zhou D, Srivastava R, Nessler S, Grummel V, Sommer N, Bruck W, et al. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc Natl Acad Sci U S A. 2006;103:19057-62 pubmed..Overall these findings suggest a pathogenic antibody response to native MOG in a subgroup of MS patients. ..
- D Alfonso S, Bolognesi E, Guerini F, Barizzone N, Bocca S, Ferrante D, et al. A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy. Genes Immun. 2008;9:7-15 pubmed..In conclusion, MOG V142L, or an untested variant in tight-linkage disequilibrium with it, is an independent MS susceptibility-modulating factor in the HLA class I region. ..
- Milward E, Kim K, Szklarczyk A, Nguyen T, Melli G, Nayak M, et al. Cleavage of myelin associated glycoprotein by matrix metalloproteinases. J Neuroimmunol. 2008;193:140-8 pubmedDerivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth...
- Eltayeb S, Sunnemark D, Berg A, Nordvall G, Malmberg A, Lassmann H, et al. Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease. J Neuroimmunol. 2003;142:75-85 pubmed..Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model. ..
- Venkatesh K, Chivatakarn O, Lee H, Joshi P, Kantor D, Newman B, et al. The Nogo-66 receptor homolog NgR2 is a sialic acid-dependent receptor selective for myelin-associated glycoprotein. J Neurosci. 2005;25:808-22 pubmed
- Henley J, Huang K, Wang D, Poo M. Calcium mediates bidirectional growth cone turning induced by myelin-associated glycoprotein. Neuron. 2004;44:909-16 pubmed..Thus, distinct Ca2+ signaling, which can be modulated by cAMP, mediates the bidirectional turning responses induced by MAG. ..
- Ogata T, Iijima S, Hoshikawa S, Miura T, Yamamoto S, Oda H, et al. Opposing extracellular signal-regulated kinase and Akt pathways control Schwann cell myelination. J Neurosci. 2004;24:6724-32 pubmed..Our results also propose the possibility of augmenting Schwann cell functions by modulating intracellular signals in light of future cell therapies. ..
- Spencer T, Filbin M. A role for cAMP in regeneration of the adult mammalian CNS. J Anat. 2004;204:49-55 pubmed..When activated, these signalling pathways can induce axonal regeneration in the presence of the myelin-associated inhibitors both in vitro and in vivo. ..
- Delarasse C, Daubas P, Mars L, Vizler C, Litzenburger T, Iglesias A, et al. Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. J Clin Invest. 2003;112:544-53 pubmed..This total lack of immune tolerance to MOG in WT C57BL/6 mice may be responsible for the high pathogenicity of the anti-MOG immune response as well as the high susceptibility of most animal strains to MOG-induced EAE. ..
- Fex Svenningsen A, Shan W, Colman D, Pedraza L. Rapid method for culturing embryonic neuron-glial cell cocultures. J Neurosci Res. 2003;72:565-73 pubmed..No overgrowth of fibroblasts or other nonneuronal cells was noted in any cultures, and myelination of the peripheral nervous system and central nervous system cultures was very robust. ..
- Bourquin C, Schubart A, Tobollik S, Mather I, Ogg S, Liblau R, et al. Selective unresponsiveness to conformational B cell epitopes of the myelin oligodendrocyte glycoprotein in H-2b mice. J Immunol. 2003;171:455-61 pubmed
- Breithaupt C, Schubart A, Zander H, Skerra A, Huber R, Linington C, et al. Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein. Proc Natl Acad Sci U S A. 2003;100:9446-51 pubmed..Our data provide the structural basis for the development of diagnostic and therapeutic strategies targeting the pathogenic autoantibody response to MOG. ..
- Clements C, Reid H, Beddoe T, Tynan F, Perugini M, Johns T, et al. The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis. Proc Natl Acad Sci U S A. 2003;100:11059-64 pubmed..The structure of this key autoantigen suggests a relationship between the dimeric form of MOG within the myelin sheath and a breakdown of immunological tolerance to MOG that is observed in multiple sclerosis. ..
- Marta C, Montano M, Taylor C, Taylor A, Bansal R, Pfeiffer S. Signaling cascades activated upon antibody cross-linking of myelin oligodendrocyte glycoprotein: potential implications for multiple sclerosis. J Biol Chem. 2005;280:8985-93 pubmed..Oligodendrocyte survival is not compromised by these treatments. We discuss the possible significance of the anti-MOG-induced signaling cascade in relation to the initial steps of MOG-mediated demyelination. ..
- Sicotte M, Tsatas O, Jeong S, Cai C, He Z, David S. Immunization with myelin or recombinant Nogo-66/MAG in alum promotes axon regeneration and sprouting after corticospinal tract lesions in the spinal cord. Mol Cell Neurosci. 2003;23:251-63 pubmed..This work shows, however, that axon growth inhibitors in myelin can be selectively blocked using this immunization approach to promote long-distance axon regeneration in the spinal cord. ..
- Wefer J, Harris R, Lobell A. Protective DNA vaccination against experimental autoimmune encephalomyelitis is associated with induction of IFNbeta. J Neuroimmunol. 2004;149:66-76 pubmed..We suggest that the underlying mechanism of DNA vaccination is associated with immunomodulation exerted by induced IFNbeta. ..
- Mi S, Lee X, Shao Z, Thill G, Ji B, Relton J, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci. 2004;7:221-8 pubmed..This effect on neurons was mimicked using an exogenously added human LINGO-1-Fc fusion protein. Together these observations suggest that LINGO-1 has an important role in CNS biology. ..
- Filbin M. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci. 2003;4:703-13 pubmed
- Pagany M, Jagodic M, Schubart A, Pham Dinh D, Bachelin C, Baron van Evercooren A, et al. Myelin oligodendrocyte glycoprotein is expressed in the peripheral nervous system of rodents and primates. Neurosci Lett. 2003;350:165-8 pubmed
- Sunnemark D, Eltayeb S, Wallstrom E, Appelsved L, Malmberg A, Lassmann H, et al. Differential expression of the chemokine receptors CX3CR1 and CCR1 by microglia and macrophages in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis. Brain Pathol. 2003;13:617-29 pubmed..This has great relevance for the possibility of therapeutic intervention in demyelinating diseases such as multiple sclerosis, for example by targeting signaling events leading to monocyte recruitment. ..
- Bettelli E, Pagany M, Weiner H, Linington C, Sobel R, Kuchroo V. Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. J Exp Med. 2003;197:1073-81 pubmed
- Pagany M, Jagodic M, Bourquin C, Olsson T, Linington C. Genetic variation in myelin oligodendrocyte glycoprotein expression and susceptibility to experimental autoimmune encephalomyelitis. J Neuroimmunol. 2003;139:1-8 pubmed..These results suggest that differences in the expression of MOG in the target organ, rather than in the immune system may influence susceptibility to MOG-EAE. ..
- Pelayo R, Tintore M, Montalban X, Rovira A, Espejo C, Reindl M, et al. Antimyelin antibodies with no progression to multiple sclerosis. N Engl J Med. 2007;356:426-8 pubmed
- Bettini M, Rosenthal K, Evavold B. Pathogenic MOG-reactive CD8+ T cells require MOG-reactive CD4+ T cells for sustained CNS inflammation during chronic EAE. J Neuroimmunol. 2009;213:60-8 pubmed publisher..CD8+ T cells reactive to MOG37-46 are pro-inflammatory and traffic to the CNS; however, the presence of CD4+ T cells elicits more severe disease and sustained inflammation of the CNS. ..
- Garces Sanchez M, Dyck P, Kyle R, Zeldenrust S, Wu Y, Ladha S, et al. Antibodies to myelin-associated glycoprotein (anti-Mag) in IgM amyloidosis may influence expression of neuropathy in rare patients. Muscle Nerve. 2008;37:490-5 pubmed publisher..They do not appear to affect the occurrence or expression of polyneuropathy, except possibly in occasional cases with WB positivity...
- Pernet V, Joly S, Christ F, Dimou L, Schwab M. Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation. J Neurosci. 2008;28:7435-44 pubmed publisher..Together, our results demonstrate that Nogo-A and MAG are differently involved in oligodendrocyte maturation in vivo, and suggest that Nogo-A may influence also remyelination in pathological conditions such as multiple sclerosis. ..
- Sättler M, Demmer I, Williams S, Maier K, Merkler D, Gadjanski I, et al. Effects of interferon-beta-1a on neuronal survival under autoimmune inflammatory conditions. Exp Neurol. 2006;201:172-81 pubmed..We conclude that IFN-beta-1a is a suitable candidate to be combined with a directly neuroprotective agent in order to further decrease axonal and neuronal degeneration in MS patients. ..
- Mannie M, Swanborg R, Stepaniak J. Experimental autoimmune encephalomyelitis in the rat. Curr Protoc Immunol. 2009;Chapter 15:Unit 15.2 pubmed publisher..This unit also provides a brief discussion of the basic characteristics of these models. ..
- Isaksson M, Ardesjö B, Rönnblom L, Kämpe O, Lassmann H, Eloranta M, et al. Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE. Eur J Immunol. 2009;39:2925-35 pubmed publisher..In contrast, pDC depletion a week after MOG immunization resulted in more severe clinical signs of EAE. In conclusion, we demonstrate that pDC promote initiation of MOG-induced Th17-cell responses and EAE. ..
- Kaushansky N, Eisenstein M, Zilkha Falb R, Ben Nun A. The myelin-associated oligodendrocytic basic protein (MOBP) as a relevant primary target autoantigen in multiple sclerosis. Autoimmun Rev. 2010;9:233-6 pubmed publisher..Accordingly, the MOBP should be considered a bona fide primary target antigen in MS, in addition to MBP, PLP, and MOG. ..
- Iruretagoyena M, Riedel C, Leiva E, Gutierrez M, Jacobelli S, Kalergis A. Activating and inhibitory Fcgamma receptors can differentially modulate T cell-mediated autoimmunity. Eur J Immunol. 2008;38:2241-50 pubmed publisher..These findings suggest that the balance between activating and inhibitory FcgammaR signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression. ..
- Ghiani C, Ying Z, de Vellis J, Gomez Pinilla F. Exercise decreases myelin-associated glycoprotein expression in the spinal cord and positively modulates neuronal growth. Glia. 2007;55:966-75 pubmed..Overall, these results show that exercise promotes a permissive cellular environment for axonal growth in the adult spinal cord requiring BDNF action. ..
- Merkler D, Böscke R, Schmelting B, Czeh B, Fuchs E, Bruck W, et al. Differential macrophage/microglia activation in neocortical EAE lesions in the marmoset monkey. Brain Pathol. 2006;16:117-23 pubmed..Our findings indicate that the inflammatory response, especially macrophage and microglia activation, may be regulated differently in gray matter areas in primate brain. ..
- Yamashita T, Hata K, Yamaguchi A, Kubo T. [Regeneration and plasticity of the injured central nervous system]. Tanpakushitsu Kakusan Koso. 2007;52:11-7 pubmed
- Zaheer A, Zaheer S, Sahu S, Yang B, Lim R. Reduced severity of experimental autoimmune encephalomyelitis in GMF-deficient mice. Neurochem Res. 2007;32:39-47 pubmed..Our results show a significant decrease in incidence, delay in onset, and reduced severity of EAE in GMF-deficient mice, and support the hypothesis that GMF plays a major role in the pathogenesis of disease. ..
- Bannerman P, Hahn A, Ramirez S, Morley M, Bonnemann C, Yu S, et al. Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice. Brain. 2005;128:1877-86 pubmed..We hypothesize that these motor neuron abnormalities contribute to weakness in this form of EAE and speculate that similar motor neuron abnormalities are present in patients with progressive multiple sclerosis...
- Haas J, Hug A, Viehöver A, Fritzsching B, Falk C, Filser A, et al. Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur J Immunol. 2005;35:3343-52 pubmed..The effect was persistent and not due to responder cell resistance or altered survival of Treg, suggesting that a defective immunoregulation of peripheral T cells mediated by (CD4+)CD25high T lymphocytes promotes CNS autoimmunity in MS. ..
- von Büdingen H, Menge T, Hauser S, Genain C. Restrictive and diversifying elements of the anti-myelin/oligodendrocyte glycoprotein antibody response in primate experimental allergic encephalomyelitis. Immunogenetics. 2006;58:122-8 pubmed..These results are the first to contribute to a better understanding of how myelin-directed and potentially destructive autoantibody responses may develop in human MS. ..
- Defaux A, Zurich M, Honegger P, Monnet Tschudi F. Inflammatory responses in aggregating rat brain cell cultures subjected to different demyelinating conditions. Brain Res. 2010;1353:213-24 pubmed publisher..These findings indicate that each of the three demyelinating insults caused distinct patterns of demyelination and inflammatory reactivity, and that of the demyelinating agents tested only LPC exhibited general toxicity. ..