The role of CXCL12, its receptors and signaling pathways in axonal regeneration in the central nervous system

中枢神经系统（CNS）的神经元通常不能再生受损的轴突。这种再生失败是由于中枢神经系统髓磷脂和损伤部位胶质瘢痕形成的抑制分子以及成熟神经元再生轴突的内在能力不足。我们已发表和未发表的数据表明，CXCL12可以促进原代神经元轴突的生长，并发挥去抑制作用，从而促进脊髓损伤后轴突的生长。然而，CXCL12这些有益作用的机制尚不清楚。本拨款提案通过确定功能受体、关键的下游信号通路和CXCL12相互作用的亚细胞位点来解决这一问题。此外，我们将测试CXCL12作为促进受损视神经轴突再生因子的潜力。这项研究计划包括药理学和遗传学方法，并使用细胞培养模型和两种体内再生范例。

Neurons of the central nervous system (CNS) normally fail to regenerate injured axons. This regenerative failure is due to inhibitory molecules of the CNS myelin and glial scar forming at the injury site as well as an insufficient intrinsic capability of mature neurons to regrow axons. As shown by our published and unpublished data CXCL12 enhances axon growth of primary neurons and exerts disinhibitory effects, resulting in enhanced axon growth after spinal cord injury. However, the mechanisms underlying these beneficial effects of CXCL12 are still un-known. This grant proposal addresses this issue by identifying the functional receptor(s), the critical downstream signaling pathways, and subcellular sites of CXCL12 interaction. Moreover, we will test the potential of CXCL12 as a factor promoting axonal regeneration in the injured optic nerve. This research proposal involves pharmacological as well as genetic approaches and uses cell culture models and two in vivo regeneration paradigms.