Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination
Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination
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DOI：
10.1038/nn1319
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发表时间：
2004-10-01
影响因子：
25
通讯作者：
Power, C
中科院分区：
文献类型：
--
作者：
Antony, JM;van Marle, G;Power, C
人类内源性逆转录病毒（HERVs）占人类基因组的8%，并且与健康和疾病都有关系。在免疫激活的神经胶质细胞中，HERV基因活性增加，尽管HERV在神经系统中表达的后果仍不确定。在此，我们报道在多发性硬化症患者的急性脱髓鞘病变内的神经胶质细胞中，HERV - W编码的糖蛋白合胞素上调。星形胶质细胞中合胞素的表达诱导氧化还原反应物的释放，其对少突胶质细胞具有细胞毒性。在多发性硬化症小鼠模型中，抗氧化剂阿魏酸可阻止合胞素介导的神经炎症和少突胶质细胞死亡以及随之而来的神经行为缺陷。因此，合胞素在神经系统中的促炎特性表明一种内源性逆转录病毒蛋白具有新的作用，它可能是治疗干预的靶点。
Human endogenous retroviruses (HERVs) constitute 8% of the human genome and have been implicated in both health and disease. Increased HERV gene activity occurs in immunologically activated glia, although the consequences of HERV expression in the nervous system remain uncertain. Here, we report that the HERV-W encoded glycoprotein syncytin is upregulated in glial cells within acute demyelinating lesions of multiple sclerosis patients. Syncytin expression in astrocytes induced the release of redox reactants, which were cytotoxic to oligodendrocytes. Syncytin-mediated neuroinflammation and death of oligodendrocytes, with the ensuing neurobehavioral deficits, were prevented by the antioxidant ferulic acid in a mouse model of multiple sclerosis. Thus, syncytin's proinflammatory properties in the nervous system demonstrate a novel role for an endogenous retrovirus protein, which may be a target for therapeutic intervention.