Disease relevance of Mog

• Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is a target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis [1].
• The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin [2].
• Strikingly, the only sequence identical to DHSYQEE was found in a Chlamydia trachomatis protein of unknown function, raising the possibility that Chlamydia infections may play a role in the MOG-specific autoimmune response in man [2].
• The data provide a strong link between in vivo and in vitro observations regarding demyelinating disease, further indicate a biochemical mechanism for anti-MOG-induced demyelination, and suggest in vitro tools for determining autoimmune antibody pathogenicity in multiple sclerosis patients [3].
• In the present study we actively induced MOG-experimental autoimmune encephalomyelitis (EAE) in different inbred rat strains using different immunization protocols [4].

High impact information on Mog

• Treating mice with monoclonal antibodies against Sema4A blocks the development of an experimental autoimmune encephalomyelitis that is induced by an antigenic peptide derived from myelin oligodendrocyte glycoprotein [5].
• However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat [6].
• Potentially lethal EAE is mediated by myelin basic protein (MBP)-specific T cells in Lewis rats, whereas transfer of S100beta- or myelin oligodendrocyte glycoprotein (MOG)-specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease [6].
• Rather, it determines the degree of disease susceptibility, recruitment of MOG-specific immunocompetent cells, clinical course, and CNS pathology in a hierarchical and allele-specific manner [7].
• Nonpathogenic IgGs bound recombinant mouse MOG and deglycosylated MOG in myelin (tested by Western blot), but only pathogenic IgGs bound glycosylated MOG [3].

Chemical compound and disease context of Mog

• Action of treosulfan in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis and human lymphocytes [8].
• Pioglitazone, a selective PPAR-gamma agonist, partially protected aggregates from anti-MOG demyelination [9].
• In our present study, we investigated effects of simvastatin treatment on degeneration of retinal ganglion cell (RGC) bodies as well as their axons during MOG-induced optic neuritis [10].
• Functional and histo pathological data of retinal ganglion cells and optic nerves revealed that neuron and axon protection was most effective when erythropoietin treatment that was started at immunization was combined with high-dose methylprednisolone therapy given from days 1 to 3 of MOG-induced experimental autoimmune encephalomyelitis [11].

Biological context of Mog

• We colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22 [1].
• The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions [1].
• The antibody 8-18C5 binds to three loops located at the membrane-distal side of MOG with a surprisingly dominant contribution made by MOG residues 101-108 containing a strained loop that forms the upper edge of the putative ligand binding site [2].
• Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane-spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members [12].
• The rat MOG sequence spanning amino acids 35-55 [rMOG-(35-55)-peptide] differs from the human sequence [hMOG-(35-55)-peptide] by a single amino acid substitution, i.e. Pro42-->Ser [13].

Anatomical context of Mog

• Oligodendrocyte progenitor cells in the adult rat CNS express myelin oligodendrocyte glycoprotein (MOG) [14].
• Double immunofluorescence revealed colocalization of NG2 and MOG on cells in the normal adult rat spinal cord [14].
• These data demonstrate that EAE can be induced in C57BL/6 mice by two mechanisms, depending on the nature of the immunogen: an encephalitogenic T cell response to rat MOG or rodent MOG 35-55, or an encephalitogenic B cell response to epitopes on human MOG protein that most likely cross-react with mouse determinants [15].
• In contrast, human MOG protein-induced EAE was B cell dependent with polymorphonuclear leukocytes [15].
• BMT resulted in increased numbers of CD4(+)CD25(bright) regulatory T cells, increased Foxp3 expression, a shift in T-cell epitope recognition, and a strong reduction of autoantibodies even after rechallenge with MOG [16].

Associations of Mog with chemical compounds

• Human MOG 35-55 was only weakly encephalitogenic, and a proline substitution in rat MOG at position 42 severely attenuated its encephalitogenicity [15].
• Specifically, substituting proline at position 42 with serine in human MOG (as in rat MOG) eliminates the B cell requirement for EAE [3].
• A panel of 13 monoclonal antibodies (mAbs) has been raised to the central nervous system-specific glycoprotein, myelin oligodendrocyte glycoprotein; five of these mAbs recognize a carbohydrate epitope on the molecule [17].
• We here explored the efficacy of treosulfan in the treatment of MOG-induced EAE in DA rats [8].
• Therefore, pioglitazone protection seems to be linked to an inhibition of glial cell proinflammatory activities following anti-MOG induced demyelination [9].

Regulatory relationships of Mog

• Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18 [18].

Other interactions of Mog

• In the present study, we show that, in rats suffering from myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis, systemic application of erythropoietin (Epo) significantly increased survival and function of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve [19].
• Differential expression of the chemokine receptors CX3CR1 and CCR1 by microglia and macrophages in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis [20].
• We show here that induction of experimental autoimmune encephalomyelitis (EAE) by myelin oligodendrocyte glycoprotein (MOG) resulted in a profound decrease in GRK2 and GRK6 protein in splenocytes during all phases of disease [21].
• We recently published evidence that a subpopulation of myelin oligodendrocyte glycoprotein (MOG)-expressing cells in the adult rat spinal cord co-expressed molecules previously considered to be restricted to oligodendrocyte progenitors [G. Li et al. (2002) Brain Pathol., 12, 463-471] [22].
• Antibodies against myelin basic protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin oligodendrocyte glycoprotein were used, and the density of the antibody-positive fibers was classified into five categories [23].

Analytical, diagnostic and therapeutic context of Mog

• Serial lectin affinity chromatography of 14C-glycopeptides indicated that MOG N-oligosaccharide structures are mainly of the complex type, accounting for 77.8% of total radioactivity [24].
• Myelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis [12].
• All MOG proteins analyzed induced high titers of anti-MOG (tested by ELISA), but only antisera from mice immunized with unmodified human MOG were encephalitogenic in primed B cell-deficient mice [3].
• Microinjection of an antibody to myelin oligodendrocyte glycoprotein (MOG) and complement was employed to generate circumscribed areas of demyelination in the adult rat spinal cord [25].
• Experimental autoimmune encephalomyelitis (EAE) induced by active immunization with the myelin oligodendrocyte glycoprotein (MOG) is an Ab-mediated, T cell-dependent autoimmune disease that replicates the inflammatory demyelinating pathology of multiple sclerosis [26].

References