Myelin inhibitors

Nogo-A neutralizing antibodies lead to axonal growth and functional recovery in vivo. After cell culture experiments, the next step was to show the ability to block myelin inhibitors and achieve axonal regrowth after spinal cord injury. The monoclonal antibody IN-1 was initially raised against myelin fractions enriched for... 

Nye JS, Voglmaier S, Martenson RE, Snyder SH. Myelin basic protein is an endogenous inhibitor of the high affinity cannabinoid binding site in brain. J Neurochem 1988 50 1170-1178. 

Filbin, M. T. Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat. Rev. Neurosci. 4, 703-713, 2003. 

Nogo-A is a potent inhibitor of neurite growth and blocks axonal regeneration in the central nervous system. Early in vitro experiments showed that neurite outgrowth was impeded across a culture dish coated with CNS myelin whereas neurites would actively grow on a... 

Chen, M. S., Huber, A. B., Van Der Haar, M. E. etal. Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403 434-439, 2000. 

Figure 2.11. The dependence of the position of the fluorescence spectrum maximum on excitation wavelength for tryptophan in a model medium (glycerol) at different temperatures (a) and singletryptophan proteins (b). 1, Whiting parvalbumin, pH 6.S in the presence of Ca2+ ions 2, ribonuclease Th pH 6.5 3, ribonuclease C2, pH 6.5 4, human serum albumin, pH 7.0, +10"4 M sodium dodecyl sulfate 5, human serum albumin, pH 3.2 6, melittin, pH 7.5, +0.15 M NaCl 7, protease inhibitor IT-AJ from Actinomyces janthinus, pH 2.9 8, human serum albumin, pH 7.0 9, -casein, pH 7.5 10, protease inhibitor IT-AJ, pH 7.0 11, basic myelin protein, pH 7.0 12, melittin in water. The dashed line is the absorption spectrum of tryptophan.

Organotellurium compounds such as dimethyltellurium dichloride and dimethyltelluride have been reported as potential inhibitors of squalene monooxygenase, causing a dramatic reduction in the rate of cholesterol biosynthesis and leading to degradation of the myelin sheath. 

One possible explanation for the lack of oxidation by galactose oxidase was thought to be steric hindrance. To investigate this possibility, lyophilized myelin containing 5.45 mg protein in 5 ml 0.1 M phosphate buffer, pH 7.4, was mixed with 0.5 ml of the same buffer solution containing 1400 units of trypsin and incubated for 1 h at 37°C. 5 mg Of trypsin inhibitor in 1 ml of... 

Analysis of congenital hypomyelinat-ing Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. Proc Natl Acad Sci USA 102, 2596-2601. 

The breakdown and dissolution of myelin in multiple sclerosis also may be related to muscular dystrophy and emphysema. Multiple sclerosis has been attributed to the action of proteases, some of which are highly elevated in and around the plaques of multiple sclerosis (19). Again, the proteases responsible and their natural inhibitors are not known. 

Rossi, C. et al. 2007. Identifying druglike inhibitors of myelin-reactive T cells by phenotypic high-throughput screening of a small-molecule library. J. Biomol. Screen. 12, 481 -89. 

The latest identified myelin-specific inhibitor of axonal regeneration is the oHgodendrocyte-myelin glycoprotein (OMgp). Like NgR, OMgp is a GPI anchored LRR protein containing eight LRRs and a LRRNT subdomain... 

Caroni, P., and Schwab, M. E. (1988). Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1, 85-96. 

---