Миелин негізгі ақуызы және демиелинизация аурулары

Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the nervous system. The myelin sheath is a multi layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction. MBP maintains the correct structure of myelin, interacting with the lipids in the myelin membrane. MBP was initially sequenced in 1971 after isolation from bovine myelin membranes. At protein level, the concentration of MBP in the CNS is tenfold higher in sections of white matter compared with cerebral cortex.

Myelin basic protein has been classified as an intrinsically disordered protein that has no stable secondary structure in solution. Like most IDPs, it has a high net charge and a low mean hydrophobicity, minimizing the hydrophobic effect that drives traditional protein folding. It does contain some exceptions to normal IDP amino acid content. For example, MBP has more arginine and less glutamic acid than most IDPs. However, this is likely because those changes are necessary for MBP to be sufficiently basic and positively charged to correctly interact with the membrane. Notably, MBP has been shown to adopt a more stable secondary structure on interaction with lipids. NMR and Cys specific spin labeling experiments have predicted this structure to contain beta sheet and regions of amphipathic helix. As implied by its name, myelin basic protein is significantly basic, with an isoelectric point of 10. It is thought to associate with the cell membrane through electrostatic interactions between its positive charges and negatively charged phospholipid heads of the plasma membrane. These modifications include phosphorylation, methylation, deamidation, citrullination, ADP ribosylation, and N terminal acylation C1 is the least modified, while C8 is the most distinct, containing 6 11 additional citrullinations. Since each of these decreases its positive charge, C8 has the smallest net positive charge of the isomers. Alternations in these post translational modifications have been associated with demyelinating diseases. Notably, MBP isolated from individuals with multiple sclerosis have had a higher degree of citrullination and a smaller positive charge. In a rare, severe form of MS known as Marburg's syndrome, the citrullination was even more extensive.

Interest in MBP has centered on its role in demyelinating diseases, in particular, multiple sclerosis (MS). The target antigen of the autoimmune response in MS has not yet been identified. However, several studies have shown a role for antibodies against MBP in the pathogenesis of MS. It is able to show that T cells were activated by this peptide. These activated T cells also recognized and initiated an immune response against a synthetically created peptide sequence that is identical to part of human MBP. During their research, they found that the levels of these cross reactive T cells are significantly elevated in multiple sclerosis patients. Some research has shown that inoculating an animal with MBP to generate an MBP specific immune response against it increases blood–brain barrier permeability. Permeability is enhanced when the animal is inoculated against non specific proteins. A targeted immune response to MBP has been implicated in lethal rabies infection. The inoculation of MBP generates increases the permeability of the blood–brain barrier (BBB), allowing immune cells to enter the brain, the primary site of rabies virus replication. In a study of mice infected with Silver haired bat rabies virus (SHBRV), the mortality rate of mice treated with MBP improved 20% 30% over the untreated control group. It is significant to note that healthy uninfected mice treated with MBP showed an increase in mortality rate between 0% and 40%.