Myelin oligodendrocyte glycoprotein

Myelin Oligodendrocyte Glycoprotein (MOG) is a is_associated_with::glycoprotein believed to be important in the is_associated_with::myelination of is_associated_with::nerves in the is_associated_with::central nervous system (CNS). In humans this protein is encoded by the MOG is_associated_with::gene. It is speculated to serve as a necessary “adhesion molecule” to provide structural integrity to the myelin sheath and is known to develop late on the oligodendrocyte.

Molecular function
While the primary molecular function of MOG is not yet known, its likely role with the myelin sheath is either in sheath “completion and/or maintenance”. More specifically, MOG is speculated to be “necessary” as an "adhesion molecule" on the myelin sheath of the CNS to provide the structural integrity of the myelin sheath. ”

MOG’s cDNA coding region in humans have been shown to be “highly homologous” to rats, mice, and bovine, and hence highly conserved. This suggests “an important biological role for this protein”.

Physiology
The gene for MOG, found on chromosome 6p21.3-p22, was first sequenced in 1995. It is a is_associated_with::transmembrane protein expressed on the surface of oligodendrocyte cell and on the outermost surface of is_associated_with::myelin sheaths. “MOG is a quantitatively minor type I transmembrane protein, and is found exclusively in the CNS. “A single Ig-domain is exposed to the extracellular space" and consequently allows autoantibodies easy access. and therefore easily accessible for autoantibodies. The MOG “primary nuclear transcript … is 15,561 nucleotides in length" and, for humans, it has eight is_associated_with::exons which are “separated by seven is_associated_with::introns".  The introns "contain numerous reptitive [sic] DNA " sequences, among which is "14 Alu sequences within 3 introns", and have a range varying from 242 to 6484 bp.

Structure
Because of alternatively spliced from human mRNA of MOG gene forming at least nine isoforms.

The crystal structure of myelin oligodendrocyte glycoprotein was determined by x-ray diffraction at a resolution of 1.45 Angstrom, using protein from the Norway rat. This protein is 139 residues long, and is a member of the immunoglobulin superfamily. The dssp secondary structure of the protein is 6% helical and 43% beta sheet: there are three short helical segments and ten beta strands. The beta strands are within two antiparallel beta sheets that form an immunoglobulin-like beta-sandwich fold. Several features of the protein structure suggest MOG has a role as an "adhesin in the completion and/or compaction of the myelin sheath." There is a "significant strip" of electronegative charge beginning near the N-terminus and running about half the length of the molecule. Also, MOG was shown to dimerize in solution, and the shape complementarity index is high at the dimer interface, suggesting a "biologically relevant MOG dimer."

Synthesis
Developmentally, MOG is formed "very late on oligodendrocytes and the myelin sheath".

Non-inflammatory demyelinating diseases
Interest in MOG has centered on its role in is_associated_with::demyelinating diseases. Some of them are not-inflammatory, such as is_associated_with::adrenoleukodystrophy, vanishing white matter disease, and Rubella induced mental retardation.

anti-MOG in inflammatory demyelinating diseases
MOG has received much of its laboratory attention in studies dealing with MS. Several studies have shown a role for is_associated_with::antibodies against MOG in the is_associated_with::pathogenesis of MS., though most of them were written before the discovery of NMO-IgG and the NMO spectrum of diseases.

Animal models of MS, EAE, have shown that “MOG-specific EAE models (of different animal strains) display/mirror human multiple sclerosis", but basically explains the part involved in the optic neuritis These models with anti-MOG antibodies have been investigated extensively and are considered the only antibodies with demyelinating capacity but again, EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.

Anti-MOG mediated demyelination has been shown to behave similar to NMO in animal models, and currently it is considered even a biomarker against the MS diagnosis

But Anti-MOG autoimmunity has been found to be important for the seronegative NMO