Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury
Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury
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DOI：
10.1523/jneurosci.2828-04.2004
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发表时间：
2004-11-17
影响因子：
5.3
通讯作者：
Strittmatter, SM
中科院分区：
文献类型：
--
作者：
Li, SX;Liu, BP;Strittmatter, SM
成年哺乳动物中枢神经系统中受损轴突的生长在损伤后受到限制。三种髓鞘蛋白，Nogo，MAG（髓鞘相关糖蛋白）和OMgp（少突胶质细胞髓鞘糖蛋白），结合Nogo-66受体（NgR），并在体外抑制轴突生长。NgR功能的转基因或病毒阻断允许轴突在体内发芽。在这里，我们给予可溶性功能阻断NgR胞外域[aa 27-310; NgR（310）ecto]脊髓损伤大鼠。纯化的NgR（310）ecto-Fc蛋白在胸中背过度半切后鞘内递送。NgR（310）ecto-Fc处理动物中皮质脊髓和中缝脊髓纤维的轴突发芽与脊髓电传导改善和运动改善相关。可溶性NgR（310）外显促进轴突生长和运动恢复的能力证明了NgR拮抗剂在创伤性脊髓损伤中的治疗潜力。
The growth of injured axons in the adult mammalian CNS is limited after injury. Three myelin proteins, Nogo, MAG (myelin-associated glycoprotein), and OMgp ( oligodendrocyte myelin glycoprotein), bind to the Nogo-66 receptor (NgR) and inhibit axonal growth in vitro. Transgenic or viral blockade of NgR function allows axonal sprouting in vivo. Here, we administered the soluble function-blocking NgR ectodomain [aa 27-310; NgR(310)ecto] to spinal-injured rats. Purified NgR(310)ecto-Fc protein was delivered intrathecally after mid-thoracic dorsal over-hemisection. Axonal sprouting of corticospinal and raphespinal fibers in NgR(310)ecto-Fc-treated animals correlates with improved spinal cord electrical conduction and improved locomotion. The ability of soluble NgR(310)ecto to promote axon growth and locomotor recovery demonstrates a therapeutic potential for NgR antagonism in traumatic spinal cord injury.