可溶性Nogo-66受体对Nogo-66、髓鞘相关糖蛋白和少突胶质细胞髓鞘糖蛋白的阻断可促进脊髓损伤后轴突的发芽和恢复。
Blockade of Nogo-66, myelin-associated glycoprotein, and oligodendrocyte myelin glycoprotein by soluble Nogo-66 receptor promotes axonal sprouting and recovery after spinal injury.
作者信息
Li Shuxin, Liu Betty P, Budel Stephane, Li Mingwei, Ji Benxiu, Walus Lee, Li Weiwei, Jirik Adrienna, Rabacchi Sylvia, Choi Eugene, Worley Dane, Sah Dinah W Y, Pepinsky Blake, Lee Daniel, Relton Jane, Strittmatter Stephen M
机构信息
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
出版信息
J Neurosci. 2004 Nov 17;24(46):10511-20. doi: 10.1523/JNEUROSCI.2828-04.2004.
Abstract
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 midthoracic 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.
摘要
成年哺乳动物中枢神经系统（CNS）中受损轴突的生长在损伤后受到限制。三种髓磷脂蛋白，即Nogo、MAG（髓磷脂相关糖蛋白）和OMgp（少突胶质细胞髓磷脂糖蛋白），与Nogo-66受体（NgR）结合，并在体外抑制轴突生长。对NgR功能进行转基因或病毒阻断可使轴突在体内发生芽生。在此，我们将可溶性功能阻断型NgR胞外结构域[氨基酸27 - 310；NgR(310)ecto]给予脊髓损伤的大鼠。在胸段中部背侧半横断损伤后，将纯化的NgR(310)ecto-Fc蛋白经鞘内给药。在接受NgR(310)ecto-Fc治疗的动物中，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能力改善相关。可溶性NgR(310)ecto促进轴突生长和运动恢复的能力证明了NgR拮抗作用在创伤性脊髓损伤中的治疗潜力。
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