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

CXCL12及其受体和信号通路在中枢神经系统轴突再生中的作用

• 批准号: 239880337
• 负责人: Professor Dr. Dietmar Fischer
• 金额: --
• 依托单位: Zentrum für Pharmakologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/239880337?language=en
• 关键词: role; CXCL12; its; receptors; signaling

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 As shown by our published and unpublished data CXCL12 enhances axon growth of primary neurons and exerts disinhibitory effects, resulting in enhanced axon growth after spinal cord injury.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.

中枢神经系统（CNS）的神经元通常无法再生受损的轴突。这种再生失败是由于损伤部位形成的中枢神经系统髓磷脂和神经胶质疤痕的抑制分子以及成熟神经元再生轴突的内在能力不足所致。正如我们已发表和未发表的数据所示，CXCL12 增强原代神经元的轴突生长并发挥去抑制作用，导致脊髓损伤后轴突生长增强。然而，CXCL12 这些有益作用的机制仍然未知。该拨款提案通过识别功能受体、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个问题。此外，我们将测试 CXCL12 作为促进受损视神经轴突再生的因子的潜力。该研究提案涉及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。

项目成果

CXCL12/SDF-1 facilitates optic nerve regeneration

• DOI: 10.1016/j.nbd.2013.04.001
• 发表时间: 2013-07-01
• 期刊: NEUROBIOLOGY OF DISEASE
• 影响因子: 6.1
• 作者: Heskamp, Annemarie;Leibinger, Marco;Fischer, Dietmar
• 通讯作者: Fischer, Dietmar

Microglia Are Irrelevant for Neuronal Degeneration and Axon Regeneration after Acute Injury

• DOI: 10.1523/jneurosci.0584-17.2017
• 发表时间: 2017-06-21
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Hilla, Alexander M.;Diekmann, Heike;Fischer, Dietmar
• 通讯作者: Fischer, Dietmar

Studying the Role of Microglia in Neurodegeneration and Axonal Regeneration in the murine Visual System.

研究小胶质细胞在小鼠视觉系统神经变性和轴突再生中的作用

• DOI: 10.21769/bioprotoc.2979
• 发表时间: 2018
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: Hilla A;Fischer D
• 通讯作者: Fischer D