Disease relevance of MOG

• Myelin oligodendrocyte glycoprotein (MOG) induces a type of experimental autoimmune encephalomyelitis in animals which is very MS-like since there are demyelinating CNS lesions and axonal loss [1].
• Our aim was to devise a purification procedure that would yield sufficient quantities of highly purified MOG to subsequently test its potential encephalitogenic activity, as well as investigate the humoral and cell-mediated responses to this antigen in naturally occurring and experimentally induced autoimmune demyelinating diseases [2].
• CONCLUSIONS: This study confirms previous data only in a subanalysis indicating that patients with positive anti-MOG/MBP antibodies develop earlier relapses than patients who are antibody negative [3].
• Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein [4].
• To assess the interrelationship between MOG structure and the induction of autoimmune CNS diseases and to enable structure-based rational design of therapeutics, a homology model of human MOG(2-120) was constructed based on consensus residues found in immunoglobulin superfamily variable-type proteins having known structures [5].

Psychiatry related information on MOG

• Linkage disequilibrium analysis of polymorphisms in the gene for myelin oligodendrocyte glycoprotein in Tourette's syndrome patients from a Chinese sample [6].
• Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder [7].

High impact information on MOG

• Remembering MOG: autoantibody mediated demyelination in multiple sclerosis [8]?
• We found that targeting MOG peptide to DCs resulted in a novel form of peripheral T cell tolerance that was sufficiently profound to prevent autoimmune experimental acute encephalomyelitis (EAE) [9].
• To examine the role of DC regulated peripheral tolerance in a model autoimmune disease, we delivered an encephalitogenic oligodendrocyte glycoprotein (MOG) peptide to DCs in vivo [9].
• It is also observed in vivo in splenic DCs in acute myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalitis [10].
• No differences were observed in MOG-specific T and B cell responses between the two groups, indicating that a global T or B cell defect is not present in W/W(v) animals [11].

Chemical compound and disease context of MOG

• In view of the difficulties associated with the purification of MOG from brain tissues, the extracellular domain of human MOG corresponding to the N-terminal 121 amino acids was expressed in Escherichia coli as a glutathione sulfotransferase fusion protein [12].
• We hypothesize that antibody-mediated repartitioning of MOG into TX-100-insoluble glycosphingolipid-cholesterol-rich microdomains initiates specific cellular signaling that could be related to initial steps of MOG-mediated demyelination [13].
• A synthetic glycopeptide of human myelin oligodendrocyte glycoprotein to detect antibody responses in multiple sclerosis and other neurological diseases [14].

Biological context of MOG

• Partial amino acid sequence was obtained from both MOG bands separated by SDS-PAGE and electroblotted onto PVDF [2].
• Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions [15].
• Linkage study of polymorphisms in the gene for myelin oligodendrocyte glycoprotein located on chromosome 6p and attention deficit hyperactivity disorder [16].
• In experimental animal models of multiple sclerosis demyelinating antibody responses are directed against the myelin oligodendrocyte glycoprotein (MOG) [17].
• Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera [18].

Anatomical context of MOG

• A predominant T cell reactivity to MOG in MS suggests an important role for cell-mediated immune response to this antigen in the pathogenesis of MS [4].
• The greatest incidence of proliferative response by MS peripheral blood lymphocytes was to MOG, as 12 of 24 patients tested reacted and, of these, 8 reacted to MOG exclusively [4].
• Based on the inhibition of MBP degradation in the presence of EGTA and the analysis of the degradation products obtained following incubation of myelin with mAbs to GalC and MOG (8-18C5), the neutral protease involved in this antibody-induced degradation of MBP could be calcium-activated neutral protease [19].
• The location of the gene for myelin oligodendrocyte glycoprotein (MOG), in the region of 6p with the strongest evidence for linkage to RD, and its proposed role as a minor component of myelin in the central nervous system suggest that it may be a factor in neuronal functioning and therefore a candidate for RD and ADHD [16].
• Interestingly, the same peptide was presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG epitopes in the pathogenesis of human MS [20].

Associations of MOG with chemical compounds

• Consistently, oxidants and prooxidants like H(2)O(2) and diamide also markedly inhibited the expression of MOG, CNPase, and PLP [21].
• MOG-induced EAE did not occur with transfer of B cells that had been nonspecifically activated by lipopolysaccharide or isolated from naïve or myelin basic protein (MBP)-primed WT mice [22].
• Myelin oligodendrocyte glycoprotein (MOG) is a quantitatively minor glycoprotein of the CNS localized preferentially on the outermost myelin lamellae and the oligodendrocyte plasma membrane [23].
• MOG was purified by polyacrylamide gel electrophoresis, followed by electroelution [24].
• The expressed protein was localized to inclusion bodies, and varying the growth parameters resulted in the solubilization of small amounts of GST-MOG that could be affinity purified on glutathione agarose columns [12].

Regulatory relationships of MOG

• Demyelinating antibodies to myelin oligodendrocyte glycoprotein and galactocerebroside induce degradation of myelin basic protein in isolated human myelin [19].
• Both treatment groups revealed similar cytokine secretion patterns except for a more pronounced decrease of both spontaneous and MOG 14-39 induced IL-4 secretion in the IFN-beta1a treated group [25].
• Treatment with chimeric anti-human CD40 antibody suppresses MRI-detectable inflammation and enlargement of pre-existing brain lesions in common marmosets affected by MOG-induced EAE [26].
• Among controls, there were no significant changes over time in OKT3- or MOG-stimulated IFN-gamma, or in depression (P> or = .25 for all) [27].

Other interactions of MOG

• Our findings using this sample do not support the role of the MOG gene in ADHD [16].
• MOG non-specifically increased PBMC TNF-alpha and IL-1beta production in all groups [28].
• Using the recombinant human extracellular immunoglobulin domain of MOG (MOG-Ig) we have screened the sera and CSFs of 130 multiple sclerosis patients, 32 patients with other inflammatory neurological diseases (OIND), 30 patients with other non-inflammatory neurological diseases (ONND) and 10 patients with rheumatoid arthritis [17].
• The cytospots were immunocytochemically stained with mono- and polyclonal antibodies directed against various myelin proteins (MOG, MBP, PLP) [29].
• Immunologic findings implicate MOG as a target autoantigen in multiple sclerosis [23].

Analytical, diagnostic and therapeutic context of MOG

• Accordingly, northern blot analyzes with cDNA probes corresponding to the coding region or the 3' untranslated Alu-containing sequence revealed a single band of 2 kb, rather than the 1.6 kb of bovine, rat, or mouse MOG cDNA(s) [30].
• Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of total cellular RNA isolated from both fetal and adult human central nervous system (CNS) tissues reveals a complex array of alternatively spliced MOG-specific variants and the presence of two novel exons [31].
• We examined autoantibody responses to myelin (MBP, MOG with isotypes and epitopes) and astroglial (S100beta) antigens in four patients with NMO by ELISA and Immunoblot [32].
• At base line, serum samples were collected to test for anti-MOG and anti-MBP antibodies with Western blot analysis, and the lesions detected by cerebral MRI were quantified [33].
• At 6 months post-vaccination, 3 of the 4 anti-MOG reactive cases before vaccination and 7 of the 24 (29%) of the anti-MOG reactive cases at 3 months post-vaccination had lost their reactivity to MOG5-24 [34].

References