Myelin basic protein multiple sclerosis

Kim, J. K., Mastronardi, F. G., Wood, D. D. etal. Multiple sclerosis an important role for post-translational modifications of myelin basic protein in pathogenesis. Mol. Cell. Proteomics 2 453-462, 2003. 

The intramuscular injection of naked pDNA has also been evaluated for therapy of EAE, a mouse model of multiple sclerosis. The disease is induced in mice by s.c. injection of myelin basic protein (MBP) or proteolipid protein (PLP). In a recent study, mice were injected i.m. with pDNA encoding either IL-4/IgG or TGF / 48 hours prior to each MBP injection (on days zero and seven) (Piccirillo and Prud -homme, 1999). The disease severity was 70% lower in the IL-4/IgG or TGF / -treated mice and the mean clinical scores were significantly reduced in both groups. In addition, the IL-4 and TGF -treated mice had significantly reduced CNS inflammation, reduced T cell proliferative responses to MBP and low levels of the Th 1 cytokines IL-12 and IFN7. Thus, the pDNA therapy appeared to shift the mice to a Th2 response, which was therapeutic and reduced the severity of the disease. 

Molecular Negativity May Underlie Multiple Sclerosis Role of the Myelin Basic Protein Family in the Pathogenesis of MS Abdiwahab A. Musse and George Harauz... 

T. G., Doronin, B.M. et al.. Hydrolysis of myelin basic protein by polyclonal catalytic IgGs from the sera of patients with multiple sclerosis, J. Cell. Mol. Med. 8, 359-368, 2004 Raul, S., Nishiyama, Y, Rlanque, S. 

EAE experimental allergic/autoimmune encephalitis is an animal model for demyelinating diseases, such as multiple sclerosis. It is induced by injection of myelin basic protein or whole CNS tissue together with adjuvants. 

Wajgt A, Gorny M (1983) CSF antibodies to myelin basic protein and to myelin-associated glycoprotein in multiple sclerosis. Evidence of the intrathecal production of antibodies. Acta Neurol Scand 68 337-343. 

Holmoy T, Kvale EG, Vartdal F (2004) Cerebrospinal fluid CD4-I-T cells from a multiple sclerosis patient cross-recognize Epstein-Barr virus and myelin basic protein. 1 Neurovirol 10 278-283. 

Tejada-Simon MV, Zang YC, Hong J, Rivera VM, Zhang JZ (2003) Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann Neurol 53 189-197. 

In an experimental model of multiple sclerosis, repeated high doses of antigen (myelin basic protein) deleted both the clinical and pathological manifestations of the disease. The effects of Varicella vaccine on 50 patients with chronic progressive multiple sclerosis have therefore been studied (3). The patients were immunized with Varicella vaccine and followed for 1 year. All were seropositive for Varicella before immunization and all had rises in Varicella antibodies after being given the vaccine. There was improvement in 14 patients, 4 became worse, and 29 were unchanged. Four patients developed mild chickenpox after immunization. No other untoward adverse effects occurred. 

Warren, K. G. and Catz, I., Relative frequency of autoantibodies to myelin basic protein and proteolipid protein in optic neuritis and multiple sclerosis cerebrospinal fluid, J. Neurol. Sci., 121, 66, 1994. 

Figure 11.7. Actipat -generated prediction profile for DRBl 1501-binding peptides from the human myelin basic protein (MBP), the major autoantigen in multiple sclerosis.

R 374 G. Harauz, N. Ishiyama, C.M.D. Hill, I.R. Bates, D.S. Libich and C. Fares, Myelin Basic Protein - Diverse Conformational States of an Intrinsically Unstructured Protein and Its Roles in Myelin Assembly and Multiple Sclerosis , Micron, 2004,35,503 R 375 R.K. Harris, NMR Crystallography. The Use of Chemical Shifts , Solid State Sci., 2004,6,1025... 

A very interesting example may be the use of Bowman-Birk Inhibitor (BBI) from soybeans in the treatment of multiple sclerosis. Proteases generated during inflammation are involved in the induction of tissue damage during inflammatory demyelination in the central nervous system. Both in vitro and ex vivo, BBI inhibited myelin basic protein-specific proliferation of lymph node cells. BBI reduced the activity of matrix metalloproteinase-2 and -9 in spleen cell supernatants and was detected in the central nervous system of treated rats. BBI suppresses experimental autoimmune encephalomyelitis, it can be administered orally, and it is safe and relatively inexpensive. It may have a therapeutic role in patients with MS (Gran et al., 2006). 

---