多发性硬化
髓鞘少突胶质细胞糖蛋白
少突胶质细胞
髓鞘
生物
脑脊髓炎
实验性自身免疫性脑脊髓炎
丝氨酸蛋白酶
髓鞘碱性蛋白
免疫学
蛋白脂蛋白1
髓鞘相关糖蛋白
祖细胞
细胞生物学
中枢神经系统
蛋白酶
神经科学
干细胞
酶
生物化学
作者
Isobel A. Scarisbrick,Sachiko I. Blaber,Claudia F. Lucchinetti,Claude P. Genain,Michael Blaber,Moses Rodriguez
出处
期刊:Brain
[Oxford University Press]
日期:2002-06-01
卷期号:125 (6): 1283-1296
被引量:115
摘要
We have identified a novel serine protease, myelencephalon‐specific protease (MSP), which is preferentially expressed in the adult CNS, and therein, is abundant in both neurones and oligodendroglia. To determine the potential activity of MSP in CNS demyelination, we examined its expression in multiple sclerosis lesions and in two animal models of multiple sclerosis: Theiler’s murine encephalomyelitis virus (TMEV) and myelin oligodendrocyte glycoprotein (MOG)‐induced experimental allergic encephalomyelitis (EAE) in marmosets. High levels of MSP were present within infiltrating mononuclear cells, including macrophages and T cells, which characteristically fill sites of demyelination, both in multiple sclerosis lesions and in animal models of this disease. The functional consequence of excess MSP on oligodendroglia was determined in vitro by evaluating the effects of recombinant MSP (r‐MSP) on oligodendrocyte survival and process number. Application of excess r‐MSP resulted in a dramatic loss of processes from differentiated oligodendrocytes, and a parallel decrease in process outgrowth from immature cells. Transfection of oligodendrocyte progenitors with an MSP–green fluorescent protein construct produced similar changes in oligodendrocyte process number. Importantly, r‐MSP did not affect oligodendrocyte survival or differentiation towards the sulphatide‐positive lineage. We further demonstrate that myelin basic protein, and to a lesser extent myelin oligodendrocyte glycoprotein, can serve as MSP substrates. These studies support the hypothesis that excess MSP, as is present in inflammatory CNS lesions, promotes demyelination.
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