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The functions of proteases related to demyelination

与脱髓鞘相关的蛋白酶的功能

基本信息

批准号：
18500260
负责人：
YOSHIDA Shigetaka
金额：
$ 2.38万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18500260/
关键词：
Serine proteases KLK6 Kallikrein Multiple sclerosis EAE KLK8 Neuropsin Protease M

项目摘要

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.

本课题研究丝氨酸蛋白酶M在脱髓鞘过程中的作用。我们得到了以下结果：1.我们分析了蛋白酶M /KLK 6基因敲除小鼠（Klk 6-KO）的表型，发现野生型和Klk 6-KO小鼠之间的行为活动没有显著差异.我们比较了中枢神经系统的细胞结构，发现基因型之间没有显着差异。我们还测量了髓鞘和CNY的主要成分髓鞘碱性蛋白（MBP）的量，发现没有显著差异。在超微结构水平上，两组间少突胶质细胞结构和髓鞘形成无差异.我们诱导了实验性过敏性脑病（EAE），一种多发性硬化症的小鼠动物模型。在该模型中，Klk 6-KO小鼠表现出较慢的疾病进展和较少的淋巴细胞广泛侵袭.对脊髓损伤后的小鼠进行分析，Klk 6-KO小鼠的后肢运动活性明显更好。Western blot分析显示脊髓损伤后Klk 6-KO脊髓中MBP蛋白明显减少。这可能是由于变性髓鞘的快速降解，但需要进一步研究.在neuropsin /Klk 8基因敲除小鼠中，中枢神经系统中Klk 6的表达没有差异。上述结果表明，蛋白酶M /Klk 6在中枢神经系统损伤后脱髓鞘过程中起重要作用。