Chen M S, Huber A B, van der Haar M E, Frank M, Schnell L, Spillmann A A, Christ F, Schwab M E
Brain Research Institute, Department of Neuromorphology, University of Zurich, Switzerland.
Nature. 2000 Jan 27;403(6768):434-9. doi: 10.1038/35000219.
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. 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.
成人大脑和脊髓通过轴突再生或代偿性纤维生长来修复损伤的能力极其有限。一种针对NI-220/250(一种对神经突生长有强大抑制作用的髓磷脂蛋白)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。在此,我们报告了nogo A的克隆,即编码NI-220/250的大鼠互补DNA。nogo基因至少编码三种主要蛋白质产物(Nogo-A、-B和-C)。重组Nogo-A可被单克隆抗体IN-1识别,并以IN-1敏感的方式抑制背根神经节的神经突生长和3T3成纤维细胞的铺展。抗Nogo-A抗体可对CNS髓磷脂和少突胶质细胞进行染色,并使背根神经节神经突在CNS髓磷脂上生长并进入视神经外植体。这些数据表明,Nogo-A是神经突生长的强大抑制剂和由少突胶质细胞产生的IN-1抗原,并且可能有助于开发新的试剂以增强CNS再生和可塑性。