The functions of proteases related to demyelination

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In this research project, we have investigated on the function of a serine proteases, protease M, to demyelination. We obtained following results:1. We analyzed the phenotype of Protease M / KLK6-knockout mice (Klk6-KO) and found no significant difference in the behavioral activity between wild-type and Klk6-KO mice.2. We compared the cellular architecture of the central nervous system and found no significant difference between the genotypes. We also measured the amount of myelin basic protein (MBP), major constituent of myelin and CNPase, and found no significant difference. In ultrastructural level, there was no difference in oligodendrocyte structure or myelination.3. We induced experimental allergic encephalopathy (EAE), an animal model of multiple sclerosis in mice. In this model, Klk6-KO mice showed slower progress of the disease and less extensive invasion of lymphocytes.4. Mice after spinal cord injury were analyzed and the resultant motion activity of the hind limb was significantly better in Klk6-KO mice. Western blot analysis revealed significantly less MBP protein in Klk6-KO spinal cord after spinal cord injury. This may due to rapid degradation of degenerated myelin but further study is needed.5. In neuropsin / Klk8 knockout mice, there was no difference in Klk6 expression in the central nervous system. However, there was marked decrease in the expression of Klk6 in the skin.The above results indicate that protease M / Klk6 play an important role during demyelination after injury to the central nervous system.