List of the antibodies.
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Unlike immature neurons and the ones from the peripheral nervous system (PNS), mature neurons from the central nervous system (CNS) cannot regenerate after injury. In the past 15 years, tremendous progress has been made to identify molecules and pathways necessary for neuroprotection and/or axon regeneration after CNS injury. In most regenerative models, phosphorylated ribosomal protein S6 (p-RPS6) is up-regulated in neurons, which is often associated with an activation of the mTOR (mammalian target of rapamycin) pathway. However, the exact contribution of posttranslational modifications of this ribosomal protein in CNS regeneration remains elusive. In this study, we demonstrate that RPS6 phosphorylation is essential for PNS and CNS regeneration in mice. We show that this phosphorylation is induced during the preconditioning effect in dorsal root ganglion (DRG) neurons and that it is controlled by the p90S6 kinase RSK2. Our results reveal that RSK2 controls the preconditioning effect and that the RSK2-RPS6 axis is key for this process, as well as for PNS regeneration. Finally, we demonstrate that RSK2 promotes CNS regeneration in the dorsal column, spinal cord synaptic plasticity, and target innervation leading to functional recovery. Our data establish the critical role of RPS6 phosphorylation controlled by RSK2 in CNS regeneration and give new insights into the mechanisms related to axon growth and circuit formation after traumatic lesion.
与未成熟神经元及外周神经系统(peripheral nervous system, PNS)来源的神经元不同,中枢神经系统(central nervous system, CNS)的成熟神经元在遭受损伤后无法实现再生。在过去15年间,学界在鉴定中枢神经系统损伤后神经保护和/或轴突再生所需的分子与通路方面取得了长足进展。在大多数再生模型中,神经元内的磷酸化核糖体蛋白S6(phosphorylated ribosomal protein S6, p-RPS6)表达上调,这通常与雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)通路的激活相关。然而,该核糖体蛋白的翻译后修饰在中枢神经系统再生中的确切作用仍不明确。在本研究中,我们证实了RPS6磷酸化对小鼠体内外周神经系统及中枢神经系统的再生至关重要。我们发现,该磷酸化过程在背根神经节(dorsal root ganglion, DRG)神经元的预处理效应中被诱导,并受p90S6激酶RSK2调控。我们的研究结果显示,RSK2可调控预处理效应,且RSK2-RPS6信号轴是该过程以及外周神经系统再生的关键环节。最后,我们证实RSK2可促进背侧柱的中枢神经系统再生、脊髓突触可塑性以及靶神经支配,进而实现功能恢复。本研究数据明确了RSK2调控的RPS6磷酸化在中枢神经系统再生中的关键作用,并为创伤性损伤后轴突生长与神经环路形成相关机制提供了新的见解。



