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一种可逆转中枢神经系统髓鞘对神经突生长抑制作用的抗神经元单克隆抗体。

An antineuronal monoclonal antibody that reverses neurite growth inhibition by central nervous system myelin.

作者信息

Lozano A M, Labes M, Roder J, Roach A

机构信息

Division of Molecular Immunology and Neurobiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

出版信息

J Neurosci Res. 1995 Oct 15;42(3):306-13. doi: 10.1002/jnr.490420304.

DOI:10.1002/jnr.490420304
PMID:8583498
Abstract

A component of adult mammalian central nervous system (CNS) myelin causes collapse of neuronal growth cones and inhibits axonal growth, properties that may be responsible for the lack of regrowth of injured axons in the CNS. The molecules and detailed mechanism through which the inhibitory activity acts are not known. To study the cellular molecules mediating the response to this inhibitor, we have used an in vitro neurite growth inhibition assay to screen a panel of monoclonal antibodies raised against rat neuronal membrane proteins, for clones capable of blocking the response. One monoclonal antibody (10D) neutralized the inhibition of neurite growth seen when primary sympathetic neurons, PC12 cells or NG108-15 cells were grown on inhibitory CNS myelin substrates, but did not promote growth on non-inhibitory substrates. 10D reacted with neuronal cells but not myelin substrate proteins. The antigen recognized by 10D appears to play a role in the interaction between neurons and their growth substrates, and is a novel candidate for a cellular receptor or associated signalling molecule mediating the response to myelin inhibitors.

摘要

成年哺乳动物中枢神经系统(CNS)髓磷脂的一种成分会导致神经元生长锥塌陷并抑制轴突生长,这些特性可能是造成中枢神经系统中受损轴突缺乏再生的原因。抑制活性发挥作用的分子和详细机制尚不清楚。为了研究介导对这种抑制剂反应的细胞分子,我们使用了一种体外神经突生长抑制试验,来筛选一组针对大鼠神经元膜蛋白产生的单克隆抗体,寻找能够阻断该反应的克隆。一种单克隆抗体(10D)可中和原代交感神经元、PC12细胞或NG108 - 15细胞在抑制性中枢神经系统髓磷脂底物上生长时所观察到的神经突生长抑制作用,但在非抑制性底物上不会促进生长。10D与神经元细胞发生反应,但不与髓磷脂底物蛋白反应。10D识别的抗原似乎在神经元与其生长底物之间的相互作用中发挥作用,并且是介导对髓磷脂抑制剂反应的细胞受体或相关信号分子的一个新候选物。

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J Neurosci. 1999 May 15;19(10):4155-68. doi: 10.1523/JNEUROSCI.19-10-04155.1999.