MOG | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | MOG , BTN6, BTNL11, MOGIG2, NRCLP7, myelin oligodendrocyte glycoprotein | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 159465 MGI: 97435 HomoloGene: 111009 GeneCards: MOG | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Myelin oligodendrocyte glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene. [5] [6] [7] 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. [8]
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". [7] 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. [8] "
MOG's cDNA coding region in humans have been shown to be "highly homologous" [9] to rats, mice, and bovine, and hence highly conserved. This suggests "an important biological role for this protein". [7]
The gene for MOG, found on chromosome 6 p21.3-p22, [10] was first sequenced in 1995. It is a transmembrane protein expressed on the surface of oligodendrocyte cell and on the outermost surface of myelin sheaths. "MOG is a quantitatively minor type I transmembrane protein, [11] and is found exclusively in the CNS. "A single Ig-domain is exposed to the extracellular space" [11] and consequently allows autoantibodies easy access. and therefore is easily accessible to autoantibodies too. [7] [11] The MOG "primary nuclear transcript … is 15,561 nucleotides in length" [7] and, for humans, it has eight exons which are "separated by seven introns". [7] The introns "contain numerous reptitive[ sic ] DNA [7] " sequences, among which are "14 Alu sequences within 3 introns", [7] and have a range varying from 242 to 6484 bp.
Alternatively spliced human mRNA of the MOG gene form at least nine isoforms. [12]
The crystal structure of myelin oligodendrocyte glycoprotein was determined by x-ray diffraction at a resolution of 1.45 Angstroms, using protein from the Norway rat. This protein is 139 residues long, and is a member of the immunoglobulin superfamily. [13] The dssp secondary structure of the protein is 6% helical and 43% beta sheet: there are three short helical segments and ten beta strands. [14] The beta strands are within two antiparallel beta sheets that form an immunoglobulin-like beta-sandwich fold. [15] 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." [16]
Developmentally, MOG is formed "very late on oligodendrocytes and the myelin sheath". [8]
Interest in MOG has centered on its role in demyelinating diseases. Some of them are not-inflammatory, such as adrenoleukodystrophy, vanishing white matter disease, and Rubella induced mental retardation. [17]
MOG has received much of its laboratory attention in studies dealing with MS. Several studies have shown a role for antibodies against MOG in the pathogenesis of MS, [8] [18] though most of them were written before the discovery of NMO-IgG and the NMO spectrum of diseases.
Anti-MOG status is different depending whether it is measured by ELISA or by microarray (CBA). The proper way to identify it is by microarray, reacting patient serum with living cells, and detecting the binding IgG via a fluorescent-labeled secondary antibody. [19]
Animal models of MS, namely Experimental Autoimmune Encephalomyelitis (EAE) models, have shown that "MOG-specific EAE models (of different animal strains) display/mirror human multiple sclerosis", [8] but basically explains the part involved in the optic neuritis. [20] These models with anti-MOG antibodies have been investigated extensively and are considered the only antibodies with demyelinating capacity [8] but again, EAE pathology is closer to NMO and ADEM than to the confluent demyelination observed in MS.
Anti-MOG antibodies have been shown to behave similarly to AQP4 antibodies in animal models, [20] and are considered a biomarker against the MS diagnosis [21] [22]
Anti-MOG autoimmunity has been found to be involved in most AQP4-seronegative NMO [23] [24] and also in optic neuritis and some fulminant forms of ADEM. [25] MOG antibodies in NMOSD are variable depending on the seropositivity status. [26]
The presence of anti-MOG autoantibodies has been associated with the following conditions [27]
Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. The cause is often a trigger such as from viral infection or vaccinations.
In vertebrates, most neuronal cell axons are encased in myelin. Simply put, myelin insulates axons and increases the rate at which electrical impulses are passed along the axon. The myelinated axon can be likened to an electrical wire with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, myelin ensheaths the axon in segments: in general, each axon is encased in multiple long myelin sheaths separated by short gaps called nodes of Ranvier.
Optic neuritis describes any condition that causes inflammation of the optic nerve; it may be associated with demyelinating diseases, or infectious or inflammatory processes.
Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include:
A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their conduction ability. Consequently, this reduction in conduction can lead to deficiencies in sensation, movement, cognition, or other functions depending on the nerves affected.
Neuromyelitis optica spectrum disorders (NMOSD), including neuromyelitis optica (NMO), are autoimmune diseases characterized by acute inflammation of the optic nerve and the spinal cord (myelitis). Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients. In more than 80% of cases, NMO is caused by immunoglobulin G autoantibodies to aquaporin 4 (anti-AQP4), the most abundant water channel protein in the central nervous system. A subset of anti-AQP4-negative cases is associated with antibodies against myelin oligodendrocyte glycoprotein (anti-MOG). Rarely, NMO may occur in the context of other autoimmune diseases or infectious diseases. In some cases, the etiology remains unknown.
Experimental autoimmune encephalomyelitis, sometimes experimental allergic encephalomyelitis (EAE), is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM). EAE is also the prototype for T-cell-mediated autoimmune disease in general.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disease of the peripheral nervous system characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder is sometimes called chronic relapsing polyneuropathy (CRP) or chronic inflammatory demyelinating polyradiculoneuropathy. CIDP is closely related to Guillain–Barré syndrome and it is considered the chronic counterpart of that acute disease. Its symptoms are also similar to progressive inflammatory neuropathy. It is one of several types of neuropathy.
Multiple sclerosis is an inflammatory demyelinating disease of the CNS in which activated immune cells invade the central nervous system and cause inflammation, neurodegeneration, and tissue damage. The underlying cause is currently unknown. Current research in neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology, provide support for the notion that MS is not a single disease but rather a spectrum.
Multiple sclerosis and other demyelinating diseases of the central nervous system (CNS) produce lesions and glial scars or scleroses. They present different shapes and histological findings according to the underlying condition that produces them.
Remyelination is the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the CNS. This is a process naturally regulated in the body and tends to be very efficient in a healthy CNS. The process creates a thinner myelin sheath than normal, but it helps to protect the axon from further damage, from overall degeneration, and proves to increase conductance once again. The processes underlying remyelination are under investigation in the hope of finding treatments for demyelinating diseases, such as multiple sclerosis.
Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) due to the unknown etiology of some of them, are a heterogenous group of demyelinating diseases - conditions that cause damage to myelin, the protective sheath of nerve fibers - that occur against the background of an acute or chronic inflammatory process. IDDs share characteristics with and are often grouped together under Multiple Sclerosis. They are sometimes considered different diseases from Multiple Sclerosis, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.
Research in multiple sclerosis may find new pathways to interact with the disease, improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for multiple sclerosis. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.
Leucine rich repeat and Immunoglobin-like domain-containing protein 1 also known as LINGO-1 is a protein which is encoded by the LINGO1 gene in humans. It belongs to the family of leucine-rich repeat proteins which are known for playing key roles in the biology of the central nervous system. LINGO-1 is a functional component of the Nogo receptor also known as the reticulon 4 receptor.
Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.
Multiple sclerosis (MS) can be pathologically defined as the presence of distributed glial scars (scleroses) in the central nervous system that must show dissemination in time (DIT) and in space (DIS) to be considered MS lesions.
Chronic relapsing inflammatory optic neuropathy (CRION) is a form of recurrent optic neuritis that is steroid responsive and dependent. Patients typically present with pain associated with visual loss. CRION is a clinical diagnosis of exclusion, and other demyelinating, autoimmune, and systemic causes should be ruled out. An accurate antibody test which became available commercially in 2017 has allowed most patients previously diagnosed with CRION to be re-identified as having MOG antibody disease, which is not a diagnosis of exclusion. Early recognition is crucial given risks for severe visual loss and because it is treatable with immunosuppressive treatment such as steroids or B-cell depleting therapy. Relapse that occurs after reducing or stopping steroids is a characteristic feature.
MOG antibody disease (MOGAD) or MOG antibody-associated encephalomyelitis (MOG-EM) is an inflammatory demyelinating disease of the central nervous system. Serum anti-myelin oligodendrocyte glycoprotein antibodies are present in up to half of patients with an acquired demyelinating syndrome and have been described in association with a range of phenotypic presentations, including acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, and neuromyelitis optica.
Anti-neurofascin demyelinating diseases refers to health conditions engendered by auto-antibodies against neurofascins, which can produce both central and peripheral demyelination. Some cases of combined central and peripheral demyelination (CCPD) could be produced by them.
Anti-AQP4 diseases, are a group of diseases characterized by auto-antibodies against aquaporin 4.