Myelin oligodendrocyte glycoprotein
The myelin oligodendrocyte glycoprotein ( MOG ) is a glycoprotein, which play an important role in the process of myelination of nerves in the CNS is awarded (see also axon and conduction ). Encoded protein in humans by the MOG gene. Studies of the molecular basis of myelin formation are different for different neurological forms of the disease, in which there is a loss of the protective myelin sheath, as in multiple sclerosis.
It is believed that MOG plays a role as an adhesion molecule and thereby provides structural integrity of the myelin sheath. It is created only late in the oligodendrocytes.
- 3.1 Multiple Sclerosis
Molecular function
The primary role of molecular MOG is unknown, but most likely the one completion and / or maintenance of the myelin sheath. In detail, it is believed that MOG as " adhesion molecule " on the myelin sheath plays a role and the shell provides structural integrity. "
The cDNA coding region of the human MOG is a high degree of homology to the rat, mouse and cattle and are therefore highly conserved. This underlines the assumption that MOG plays a " biologically important role " in the organism.
Physiology
MOG gene located on chromosome 6p21.3 - p22, was sequenced in 1995.
Is a transmembrane protein that is expressed on the surface of oligodendrocytes and on the outermost layer of the myelin sheath. " MOG is a small quantity occurring in type 1 transmembrane protein that is found only in the CNS. " A single Ig domain extends into the extracellular space " and allows easy access of autoantibodies. 's Primary nuclear transcript of MOG includes ... 15.561 nucleotides " and has in man eight exons separated by seven introns ." Introns include " numerous repititive DNA " sequences, among which are a " 14 Alu sequence located within intron 3. ," the length of introns varies 242-6484 base pairs.
Structure
Due to alternative splicing of the human mRNA arising from the MOG gene at least nine isoforms.
The crystal structure of myelin oligodendrocyte glycoprotein was determined using the protein from the brown rat by X-ray crystal structure analysis with a resolution 1.45 Angstroms. The protein comprises 139 amino acids and is part of the immunoglobulin superfamily.
The DSSP secondary structure (Define Secondary Structure of Proteins ) of the protein is about 6% of helices and 43% of β -sheet: three short helical segments followed by ten β -strands. The β -sheet sequences are present which form an immunoglobulin -like β - sandwich fold within two antiparallel β -sheets. Several properties of the protein structure of the MOG suggest a role as " adhesin to complete and / or compaction of the myelin sheath. " Beginning is located near the N -terminus of a strip electro- negative charge, which stretches over half the length of the molecule. In solution, MOG has a tendency to dimerize and the "shape complementary index" is high at the dimerization junction, suggesting the existence of a " biologically relevant MOG dimer ".
Synthesis
MOG is formed only at a " relatively late date " on the oligodendrocytes and the Myleinhülle.
Diseases
The interest for MOG lies in its role in the context of demyelinating diseases such as adrenoleukodystrophy, Childhood ataxia with central Mindermyelinisierung, multiple sclerosis (MS) and rubella induced by mental retardation.
MOG is a target antigen, resulting in autoimmune demyelination. Most scientific laboratory tests to MOG are associated with MS. Various studies have shown a relationship between MOG antibodies and the pathogenesis of MS. Animal models of MS, EAE, have shown (in several animal lines ) that these EAE MOG-specific MS or similar " mirrored" almost completely. What is apparent from the capacitance and the topography of demyelinating lesions. The animal models were able to show, that are responsible for the Demyeliniserung MOG antibodies. These models have been extensively studied and MOG have been the only antibodies that have the ability to cause demyelination.
Multiple sclerosis
The exact pathogenic processes of MS are unknown, however, exist, based on the current state of knowledge, various theories: The widest recognition is currently the theory of antibody-mediated demyelination, an attack of the immune system on the body, in particular on the central nervous system, which finally to demyelination leads. According to this theory are attacked target specific antigens of the body. In detail, the T and B cells can be made as the leading to the cells in the pathogenesis of antibody-mediated demyelination of the MS is responsible. Among the several potentially involved in the pathogenesis candidates of scientific focus usually lies with the below erwähnenten studies on two antigens: One is the Myelin Basic Protein ( MBP), in which in early stages of MS already various anti- MBP antibodies are detected could. The other is the myelin oligodendrocyte glycoprotein ( MOG). Both were identified as " targets of the immune response ." In connection with the " antibody- mediating Demyelinisierungstheorie " could antibodies which are produced during the immune response, plays an important role in the pathogenesis of multiple sclerosis.
One study found a correlation between MS relapses and anti- MOG and anti -MBP antibodies in the blood serum of patients with a " clinically isolated syndrome "; these relapses resulted in patients referred ultimately to the final clinical diagnosis of MS. For both antibodies seronegative patients suffered only 23% of all cases after 45.1 ± 13.7 months, a relapse, whereas 83% of patients who had been alone tested positive for anti - MOG antibodies, within 14.6 ± 9, 6 months had a relapse. 21 of 22 patients, who had had both antibodies in the blood relapses within a period of 7.5 ± 4.4 months.
These results suggest that the occurrence of a clinically isolated syndrome consistently not necessarily have to lead to " clinically definite " MS. These results are consistent with previous data on the disease. For example, 30-40 percent of MS cases have a relatively harmless disease, which correlates with the 38 percent of patients in this study, which were negative for both antibodies. In the early course of the disease, therefore, seems to be the " antibody status " to provide an opportunity to identify patients with an expected milder disease course. The article also emphasizes the finding that these results do not prove that the antibodies cause demyelination. Rather, they provide a useful diagnostic indicator of the future course of the disease. A possible practical application of the study would be a cheaper and simpler alternative to the currently popular "Magnetic Resonance Imaging " strategy to determine the risk of relapse after a " clinically isolated syndrome ".
A similar study examined the change in risk ( a function of the antibody status ) after a previous clinically isolated syndrome to clinically definite MS develop. Examines said anti - myelin antibodies as a possible predictor of an altered risk were. While generally was diagnosed in 90 percent of patients with a clinically isolated syndrome within months to years of clinically definite MS, the results of the study also showed that patients with a negative test for the antibodies generally have a better prognosis with respect to the time of relapse had (ie, the relapse occurred generally later on ). Patients who tested positive for the antibodies were able to benefit from the earliest possible start of treatment in return due to the test. Within a period of 12 months, 30 patients were tested positive for the antibodies. 22 of these patients developed clinically definite MS. Of the patients who were negative for the antibody, whereas none developed within the said period, a clinically definite MS.
Despite these findings, other work came to the conclusion that these studies could not demonstrate conclusively that MOG actually represents one of the main contributors of the disease process of MS. MOG has demonstrated the ability to perform in vitro and in experimental animal models of demyelination. It is also demonstrated in Nervengewebsläsionen as well as in patients diagnosed with MS. Nevertheless, the significance of these findings is not yet clear manner. Two other studies were the results of the aforementioned studies confirm only in a subgroup analyzes and three other studies on the subject came to negative results. The above work provides a different interpretation of the results found: It says that the anti- MOG antibody - correlation may be at least partially reflects the cross-reactivity between MOG and the nuclear antigen of Epstein -Barr virus (EBNA ) for the development of MS. The association with MOG MS originated by its site of synthesis, which is located exclusively in the central nervous system. The true relationship between MS and MOG is still not fully understood, partly due to this lack of evidence for association between biologically active anti - MOG antibodies and demyelination, which ultimately leads to MS. Finally, while anti - MOG antibodies to determine the extent of tissue damage during the MS can be measured, they could, with the exception of biologically active antibodies, simply an accompanying phenomenon of CNS tissue degeneration represent.