Abstract
Myelin Oligodendrocyte Glycoprotein-antibody disease (MOGAD) is an immune-mediated disorder that mainly targets the central nervous system of the patient. The pattern of inflammation caused by MOGAD mainly targets the brain stem, spinal cord, and optic nerve, and the symptoms vary from person to person. Its clinical features often overlap with Multiple Sclerosis (MS) and Neuromyelitis Optica Spectrum Disorder (NMOSD) which makes the accurate diagnosis of this rare neurodegenerative disease quite difficult. Hence, this review was attempted not only to understand MOGAD but also to comprehend the differences between MOGAD and MS with the help of a brief overview of the similarities and contrasting features. Here we highlight the mechanism and importance of MOG in myelination and demyelination. Glycosylation has a serious impact on the myelination of neurons as N-glycan helps in the proper folding of MOG. On transforming into an autoantigen, MOG can activate the classical complement pathway by triggering the activation of proteins associated with the complement cascade. Patients with persistently positive antibodies to MOG are at risk for recurrent episodes of MOGAD. In the current scenario, there is an urgent need to develop therapeutic interventions that induce remyelination. Remyelination in terms of MOG glycosylation is hypothesized as a possible strategy to treat patients diagnosed with MOGAD. On the whole, the article aims to provide a clear insight into the disease and the structural aspects associated with it.
Keywords: MOG, MOGAD, demyelination, N-glycosylation, autoantigen, remyelination.
Graphical Abstract
[http://dx.doi.org/10.1002/ana.24132] [PMID: 24615937]
[http://dx.doi.org/10.1016/j.ijdevneu.2018.06.012] [PMID: 29964158]
[http://dx.doi.org/10.1006/geno.1995.1137] [PMID: 8530032]
[http://dx.doi.org/10.1007/s00401-020-02132-y] [PMID: 32048003]
[http://dx.doi.org/10.1046/j.1471-4159.1999.0720001.x] [PMID: 9886048]
[http://dx.doi.org/10.1073/pnas.1133443100] [PMID: 12874380]
[http://dx.doi.org/10.1038/s41582-018-0112-x] [PMID: 30559466]
[http://dx.doi.org/10.1111/imm.12155] [PMID: 23876060]
[http://dx.doi.org/10.1046/j.1471-4159.1995.65010309.x] [PMID: 7790876]
[http://dx.doi.org/10.1046/j.1471-4159.1996.67052219.x] [PMID: 8863536]
[http://dx.doi.org/10.1186/s40478-019-0786-3] [PMID: 31481127]
[http://dx.doi.org/10.1007/s00415-017-8583-z] [PMID: 28770374]
[http://dx.doi.org/10.1016/j.msard.2018.01.007] [PMID: 29414288]
[http://dx.doi.org/10.1212/NXI.0000000000000012] [PMID: 25340056]
[http://dx.doi.org/10.1016/B978-0-323-42876-7.00008-9]
[http://dx.doi.org/10.1523/JNEUROSCI.21-04-01302.2001] [PMID: 11160401]
[http://dx.doi.org/10.3389/fimmu.2017.00529]
[http://dx.doi.org/10.1016/S1474-4422(21)00218-0] [PMID: 34418402]
[http://dx.doi.org/10.1111/j.1471-4159.1992.tb09335.x] [PMID: 1371150]
[http://dx.doi.org/10.1517/14728222.2012.677438] [PMID: 22494461]
[http://dx.doi.org/10.1080/07391102.2021.1893816] [PMID: 33663341]
[http://dx.doi.org/10.1073/pnas.0607242103] [PMID: 17142321]
[http://dx.doi.org/10.4049/jimmunol.0801888] [PMID: 19687098]
[http://dx.doi.org/10.1083/jcb.201504106] [PMID: 26347141]
[http://dx.doi.org/10.1128/JVI.05398-11] [PMID: 21880773]
[http://dx.doi.org/10.1038/nrneurol.2013.118] [PMID: 23797245]
[http://dx.doi.org/10.1073/pnas.1807439115] [PMID: 30111543]
[http://dx.doi.org/10.1038/srep09200] [PMID: 25776265]
[http://dx.doi.org/10.1073/pnas.1833158100] [PMID: 12960396]
[http://dx.doi.org/10.4049/jimmunol.1301296] [PMID: 24014878]
[http://dx.doi.org/10.1002/jnr.23462] [PMID: 25213400]
[http://dx.doi.org/10.1016/j.jmgm.2019.107517]
[http://dx.doi.org/10.1042/BCJ20170111] [PMID: 28673927]
[PMID: 31057084]
[http://dx.doi.org/10.3389/fimmu.2019.01189]
[http://dx.doi.org/10.1084/jem.20122192] [PMID: 24935259]
[http://dx.doi.org/10.2174/1573406413666170906123204] [PMID: 28875859]
[http://dx.doi.org/10.1002/psc.2839] [PMID: 26663200]
[http://dx.doi.org/10.1016/j.jmgm.2016.06.005] [PMID: 27388119]
[http://dx.doi.org/10.4049/jimmunol.178.5.3323] [PMID: 17312184]
[http://dx.doi.org/10.3390/ijms22010100] [PMID: 33374173]
[http://dx.doi.org/10.1002/ana.25291] [PMID: 30014603]
[http://dx.doi.org/10.1097/WCO.0000000000000685] [PMID: 30893100]
[http://dx.doi.org/10.1016/0165-5728(89)90014-3] [PMID: 2649509]
[http://dx.doi.org/10.1186/s12974-018-1144-2]
[PMID: 15571060]
[http://dx.doi.org/10.1007/s13311-012-0152-7] [PMID: 23070731]
[http://dx.doi.org/10.1002/ana.1032] [PMID: 11456302]
[http://dx.doi.org/10.1212/01.WNL.0000147259.34163.33] [PMID: 15623705]
[http://dx.doi.org/10.1007/s00281-012-0308-x]
[http://dx.doi.org/10.1074/jbc.M202069200] [PMID: 11986321]
[http://dx.doi.org/10.1074/jbc.M210665200] [PMID: 12427744]
[http://dx.doi.org/10.3390/biomedicines8100410]
[http://dx.doi.org/10.1212/WNL.0000000000012467] [PMID: 34261784]
[http://dx.doi.org/10.1186/1742-2094-8-161] [PMID: 22093619]
[http://dx.doi.org/10.1007/s00415-020-10024-0] [PMID: 32623596]
[http://dx.doi.org/10.1093/brain/awaa102] [PMID: 32412053]
[http://dx.doi.org/10.1177/13524585211007086] [PMID: 33870786]
[http://dx.doi.org/10.1007/s00415-018-9122-2] [PMID: 30569382]
[http://dx.doi.org/10.1080/14712598.2018.1441284] [PMID: 29460650]
[http://dx.doi.org/10.1002/(SICI)1097-4547(19960201)43:3<273:AID-JNR2>3.0.CO;2-G] [PMID: 8714516]
[http://dx.doi.org/10.1016/0165-5728(95)00175-1] [PMID: 8642059]
[http://dx.doi.org/10.4103/1673-5374.153675] [PMID: 25878574]
[http://dx.doi.org/10.1016/j.neuron.2004.06.024] [PMID: 15260955]
[http://dx.doi.org/10.1016/j.neuron.2008.06.028] [PMID: 18760695]
[http://dx.doi.org/10.1016/j.stem.2010.04.002] [PMID: 20569695]
[http://dx.doi.org/10.1016/j.neuroscience.2006.01.055] [PMID: 16631314]
[http://dx.doi.org/10.1146/annurev-neuro-061010-113629] [PMID: 21692657]
[http://dx.doi.org/10.1021/acs.analchem.8b02664] [PMID: 30231202]
[http://dx.doi.org/10.1007/s00018-019-03327-7] [PMID: 31628495]
[http://dx.doi.org/10.1007/978-3-540-73677-6_9]
[http://dx.doi.org/10.1007/s00415-020-10026-y] [PMID: 32623595]