中枢神经再生抑制因子及免疫治疗研究

Research of regeneration inhibitors for central nervous system and immunology therapy

成体哺乳动物中枢神经损伤后早期轴突再生失败的一个主要原因是由于髓磷脂抑制分子的存在。Nogo、髓磷脂相关糖蛋白以及少突胶质细胞髓磷脂糖蛋白等神经再生抑制因子的发现,大大促进了中枢神经再生分子机制的研究。它们均能独立通过Nogo-66受体产生对轴突再生的抑制效应,髓磷脂抑制分子及其信号转导机制的研究日益成为中枢神经再生的研究热点,髓磷脂及其信号转导分子特别是Nogo-66受体、p75神经营养素受体成为损伤后促进轴突再生、抑制生长锥塌陷的主要治疗靶点。抑制上述抑制因子及相关受体NgR或p75NTR可能有助于中枢神经损伤的修复,围绕这些抑制因子及其相关受体介导的信号转导途径,人们提出了多种治疗中枢神经损伤的新思路,其中免疫学方法尤其受到关注。

One of the major obstacles to successful axon regeneration in the adult central nervous system （CNS） is the presence of inhibitory molecules which are associated with myelin. The discovery of regeneration inhibitors for CNS including Nogo, myelin associated glycoprotein （MAG） and oligodendrocyte myelin glycoprotein （OMgp）, which all can independently inhibit axon growth by binding a common receptor, the Nogo-66 receptor （NgR） has promoted the mechanism research of CNS regeneration. Myelin inhibitory molecules and the receptors, especially NgR and p75 neurotrophin receptor （p75NTR） increasingly become the hot spot in the study of CNS repair, and have become the major targets for therapeutic intervention to promote axon regeneration. Inhibition of myelin and its receptors NgR and p75NTR maybe promote the regeneration of axon after CNS injury. Around these inhibitors and associated receptors involved in the signal transduction, lots of new ways for treating spinal cord injury have been raised, especially about immunology therapy.