MOG
Description
Molecular Structure and Properties
MOG is a 139-residue protein belonging to the immunoglobulin superfamily. Key structural features include:
The extracellular Ig-domain is exposed for antibody binding, making MOG a key autoimmune target . Crystallography reveals a β-sheet-rich structure stabilized by hydrogen bonds and salt bridges .
Physiological Function
MOG is expressed late during oligodendrocyte differentiation and myelination:
MOG synthesis is developmentally regulated, with peak expression during myelin maturation . Its dimerization and electrostatic properties suggest roles in myelin compaction and stability .
Role in Autoimmune Diseases
MOG is central to MOG antibody-associated disease (MOGAD) and experimental models:
Clinical Pathogenesis
MOGAD manifests as:
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Optic neuritis (bilateral)
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Transverse myelitis (longitudinal extensive)
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ADEM-like cortical involvement
| Feature | MOGAD | MS/NMOSD |
|---|---|---|
| Antibodies | Conformational MOG-IgG | AQP4-IgG or no antibodies |
| Age of Onset | Children/young adults | Adults |
| Relapse Risk | Monophasic (common in children) | Chronic relapsing |
MOG-IgG disrupts myelin via complement activation and antibody-dependent cytotoxicity .
Experimental Autoimmune Encephalomyelitis (EAE)
MOG peptides (e.g., MOG 35–55) induce EAE in mice, mimicking MS-like demyelination . Recombinant MOG proteins (e.g., HEK293-expressed) are used to study disease mechanisms .
MOG Analogues and Pharmacological Applications
To study α-ketoglutarate (αKG)-dependent processes, MOG derivatives have been engineered:
Bulkier esters (e.g., IPOG) improve stability and reduce cytotoxicity by lowering intracellular NOG levels . These analogues are used to study MCT2 transporter pharmacophores .
Diagnostic Challenges
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Detection Methods: Cell-based assays (conformational epitopes) outperform linear ELISA .
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Prevalence: ~40% of AQP4-IgG seronegative NMOSD patients test MOG-IgG positive .
Therapeutic Targets
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B-Cell Depletion: Rituximab and ocrelizumab show efficacy in relapsing MOGAD .
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MCT2 Inhibitors: Under investigation to modulate NOG accumulation in tumors .
Future Directions
Product Specs
H-Met-Glu-Val-Gly-Trp-Tyr-Arg-Ser-Pro-Phe-Ser-Arg-Val-Val-His-Leu-Tyr-Arg-Asn-Gly-Lys-OH.
Product Science Overview
In humans, the MOG gene is located on chromosome 6 (6p22.1), while in mice, it is found on chromosome 17 . The gene was first sequenced in 1995 . The protein encoded by this gene is highly conserved across species, including humans, rats, mice, and bovines, indicating its significant biological role .
While the precise molecular function of MOG is not fully understood, it is believed to be essential for the myelination of nerves in the CNS . MOG is speculated to serve as an adhesion molecule, providing structural integrity to the myelin sheath . It is also thought to play a role in myelin maturation, myelin integrity, and cell surface interactions .
MOG has gained attention due to its involvement in inflammatory demyelinating diseases. One such condition is Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD), a rare inflammatory disease where the immune system mistakenly attacks the myelin sheath . This disease affects the optic nerves, brain, and spinal cord, leading to various neurological symptoms .
Research into MOG and its associated diseases is ongoing. Understanding the role of MOG in the CNS and its involvement in demyelinating diseases could lead to better diagnostic and therapeutic strategies. The protein’s high conservation across species makes it a valuable target for studying myelination and developing treatments for related disorders .
