Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1

Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1
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DOI:
10.1038/35000219
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发表时间:
2000-01-27
期刊:
影响因子:
64.8
通讯作者:
Schwab, ME
Schwab, ME
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chen, MS;Huber, AB;Schwab, ME

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成人大脑和脊髓通过轴突再生或补偿性纤维生长修复损伤的能力非常有限。针对NI-220/250(一种有效的神经突生长抑制剂)产生的单克隆抗体(IN-1)可促进成年大鼠中枢神经系统(CNS)损伤后的轴突再生和代偿性可塑性(1 - 4)。在这里,我们报告的nogo A,大鼠互补DNA编码NI-220/250的克隆。Nogo基因编码至少三种主要蛋白产物(Nogo-A、-B和-C),重组Nogo-A被单克隆抗体IN-1识别,并且以IN-1敏感的方式抑制背根神经节的神经突生长和3T3成纤维细胞的扩散。针对Nogo-A的抗体对中枢神经系统髓鞘和少突胶质细胞进行染色,并使背根神经节神经突起在中枢神经系统髓鞘上生长并进入视神经外植体。这些数据表明,Nogo-A是一种有效的神经突生长抑制剂和由少突胶质细胞产生的IN-1抗原,并可能允许产生新的试剂来增强CNS再生和可塑性。
The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely Limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats(1-4). Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C), Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.