LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury
LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury
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DOI：
10.1016/j.mcn.2006.08.003
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发表时间：
2006-11-01
影响因子：
3.5
通讯作者：
Relton, Jane K.
中科院分区：
文献类型：
--
作者：
Ji, Benxiu;Li, Mingwei;Relton, Jane K.
LINGO-1 是一种 CNS 特异性蛋白，也是 NgR1/p75/LINGO-1 和 NgR1/TAJ(TROY)/LINGO-1 信号复合物的功能成分，介导轴突生长的抑制。这些受体复合物通过 RhoA 激活介导 Nogo、髓磷脂相关糖蛋白 (MAG) 和少突胶质细胞髓磷脂糖蛋白 (OMgp) 的轴突生长抑制作用。可溶性 LINGO-1 (LINGO-1-Fc) 通过阻断 LINGO-1 与 NgR1 的结合而充当这些途径的拮抗剂，在脊髓背侧或外侧半切后给予大鼠。 LINGO-1-Fc 治疗可显着改善红核脊髓束或皮质脊髓束横断后的功能恢复，促进轴突出芽，减少 RhoA 激活，并增加少突胶质细胞和神经元的存活率。这些实验证明了 LINGO-1 在体内调节轴突生长中的重要作用，并且用 LINGO-1-Fc 治疗可以显着促进脊髓损伤后的恢复。 (c) 2006 Elsevier Inc. 保留所有权利。
LINGO-1 is a CNS-specific protein and a functional component of the NgR1/p75/LINGO-1 and NgR1/TAJ(TROY)/LINGO-1 signaling complexes that mediate inhibition of axonal outgrowth. These receptor complexes mediate the axonal growth inhibitory effects of Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp) via RhoA activation. Soluble LINGO-1 (LINGO-1-Fc), which acts as an antagonist of these pathways by blocking LINGO-1 binding to NgR1, was administered to rats after dorsal or lateral hemisection of the spinal cord. LINGO-1-Fc treatment significantly improved functional recovery, promoted axonal sprouting and decreased RhoA activation and increased oligodendrocyte and neuronal survival after either rubrospinal or corticospinal tract transection. These experiments demonstrate an important role for LINGO-1 in modulating axonal outgrowth in vivo and that treatment with LINGO-1-Fc can significantly enhance recovery after spinal cord injury. (c) 2006 Elsevier Inc. All rights reserved.