P2X7 receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis
P2X7 receptor blockade prevents ATP excitotoxicity in oligodendrocytes and ameliorates experimental autoimmune encephalomyelitis
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DOI：
10.1523/jneurosci.0579-07.2007
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发表时间：
2007-08-29
影响因子：
5.3
通讯作者：
Domercq, Maria
中科院分区：
文献类型：
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作者：
Matute, Carlos;Torre, Iratxe;Domercq, Maria
少突胶质细胞死亡和脱髓鞘是多发性硬化症（MS）的标志。在这里，我们表明，ATP信号可以触发少突胶质细胞兴奋性毒性，通过激活这些细胞表达的钙渗透性P2X（7）嘌呤受体。体内P2X（7）受体的持续激活引起的病变使人联想到MS斑块的主要特征，即，脱髓鞘、少突胶质细胞死亡和轴突损伤。此外，用P2X（7）拮抗剂治疗慢性实验性自身免疫性脑脊髓炎（EAE）（一种MS模型）可减少脱髓鞘并改善相关的神经症状。总之，这些结果表明ATP可以通过P2X（7）激活杀死少突胶质细胞，并且这种细胞死亡过程有助于EAE。重要的是，在MS患者中，P2X（7）表达在正常的轴突束中升高，表明在这种疾病中，通过少突胶质细胞中这种受体的信号传导可能增强。因此，P2X（7）受体拮抗剂可能对MS的治疗有益。
Oligodendrocyte death and demyelination are hallmarks of multiple sclerosis ( MS). Here we show that ATP signaling can trigger oligodendrocyte excitotoxicity via activation of calcium-permeable P2X(7) purinergic receptors expressed by these cells. Sustained activation of P2X(7) receptors in vivo causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X(7) antagonists of chronic experimental autoimmune encephalomyelitis ( EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X(7) activation and that this cell death process contributes to EAE. Importantly, P2X(7) expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X(7) receptor antagonists may be beneficial for the treatment of MS.