Myelin multiple sclerosis

The class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

Interferon beta-la (AVONEX , Rebif ), interferon beta-lb (Betaferon ), and interferon beta (Fiblaferon ) are applied in multiple sclerosis to reduce both frequency and severity of disease incidents and for the treatment of severe viral infections. In multiple sclerosis, DFN- 3 proteins modulate the destruction of myelin in the cause of the autoimmune reaction. 

Hunsperger EA, Roehrig JT (2006) Temporal analyses of the neuropathogenesis of a West Nile virus infection in mice. J Neurovirol 12 129-139 Huseby ES, Liggitt D, Brabb T, Schnabel B, Ohlen C, Goverman J (2001) A pathogenic role for myelin-specific CD8(-I-) T cells in a model for multiple sclerosis. J Exp Med 194 669-676... 

The functional significance of myelin is revealed by the neurological deficits observed in patients with multiple sclerosis. This disorder is caused by the demyelination of neurons in the brain, spinal cord, and optic nerve. The loss of myelin disrupts the normal conduction of impulses along the axons of these neurons and results in weakness, numbness, loss of bladder control, and visual disturbances. 

Antibodies typically are able to recognize peptide sequences as small as 5-6 amino acids in length. For instance, IgE auto-antibodies were found to have clinical significance in multiple sclerosis by binding specifically to short 5- and 6-amino acid epitopes on the surface of myelin proteins (Mikol et al., 2006). 

Mikol, D.D., Ditlow, C., Usatin, D., Biswas, P., Kalbfleisch, J., Milner, A., and Calenoff, E. (2006) Serum IgE reactive against small myelin protein-derived peptides is increased in multiple sclerosis patients. 

Some aspects of multiple sclerosis are reflected in the animal model experimental autoimmune encephalomyelitis, which is induced by immunization of susceptible animals with appropriate encephalogenic proteins or peptides. In these animals, if cultured adult stem cell neurospheres are injected into the bloodstream, injected cells can find their way to damaged portions of the nervous system and improve function in mice. How the injected cells augmented the recovery process is unclear. One possibility is that cells recruited to the lesions differentiated into oligodendrocytes and generated new myelin sheaths, but this seems unlikely in the face of ongoing cellular destruction. 

Iglesias, A., Bauer, J., Litzenburger, T. etal. T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36 220-234,2001. 

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. 

Multiple sclerosis 58 64% myelin oligodendrocyte glycoprotein Infectious agents (Epstein-Barr virus), solvents, ultraviolet radiation/vitamin D, tobacco... 

Oligodendrocytes are present in the CNS as well and wrap around axons to form a myelin sheath. Myelin wraps into concentric layers that spiral around the axon. Gaps in the oligodendrocytes are the nodes of Ranvier, where the membrane maintains contact with extracellular fluid. The nodes serve to propagate the action potential in myelinated axons. Schwann cells perform an analogous function, myelinating axons in the peripheral nervous system. Not all neurons are myelinated, but myelination increases the metabolic efficiency of action potentials. Demyelination of neurons produces deficits in neuronal conduction, as is seen in multiple sclerosis. 

Multiple sclerosis (MS) is a devastating disease of the CNS that produces demyelination and inflammation. It is believed that its pathogenesis involves an immune reaction against various components of the myelin sheath. In a study by Lock et al. (2002), the gene expression patterns of brain lesions obtained during autopsies of MS patients were examined by microarray cluster analysis. A total of 1080 genes (from 7026 represented... 

Multiple sclerosis (MS) is the most frequent inflammatory demyeli-nating disease of the central nervous system that affects worldwide about 2.5 million people with no cure. Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-induced EAE) in DA rats is an appropriate model for therapeutic testing, sharing many features with human multiple sclerosis. 

The molecular mechanism by which IFN-/1 induces its therapeutic effect is complex and not fully understood. It is believed that the pathology of multiple sclerosis is linked to the activation and proliferation of T lymphocytes specific for epitopes found on specific myelin antigens. Upon migration to the brain, these lymphocytes trigger an inflammatory response mediated by the production of pro-inflammatory cytokines, most notably IFN-y, IL-1, IL-2 and TNF-a. The inflammatory response, in addition to other elements of immunity (e.g. antibodies and... 

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