脊髓损伤后成熟神经元的不可再生及轴突微弱的伸长能力是限制神经功能恢复的重要因素。我们首次发现MOB1具有促进小鼠脊髓损伤后神经修复作用，体外研究证实GSK3β磷酸化MOB1 Ser146位点调控其蛋白稳定。然而，脊髓损伤后MOB1作用机制及其Ser146位点是否存在并发挥作用尚不清楚。文献报道MOB1下游LATS/NDR激酶分别参与神经干细胞分化和轴突伸长。由此，我们推测：脊髓损伤后MOB1与GSK3β结合，其Ser146磷酸化，启动其泛素化降解途径，故采用特异性单克隆抗体拮抗其Ser146磷酸化，稳定MOB1，激活下游LATS/NDR激酶，促进神经干细胞分化和轴突伸长，最终促进脊髓损伤后神经修复。项目组在前期工作的基础上，拟通过体内外实验探讨MOB1促进脊髓损伤后的内源性神经修复机制，以明确调控MOB1稳定性Ser146位点的存在及其作用，为下一步脊髓损伤治疗药物的研发提供理论依据。

The non-renewable nature and weak axonal elongation capability of mature neurons have been recognized as the important factors in restricting neural network reconstruction after spinal cord injury (SCI). We first discovered that MOB1 had a role of promoting neural repairment after SCI, and GSK3β modulated MOB1 stability via phosphorylating on its serine 146 (Ser146) in vitro. However, it is unclear how MOB1 works after SCI, and whether its Ser146 site is exist and working in vivo needs to be clarified. It was previous reported that the LATS/NDR kinase, a downstream core component of MOB1, was involved in the differentiation of neural stem cell (NSC) and axonal elongation, respectively. Based on our data and literatures, it is proposed that GSK3β binds and phosphorylates MOB1 at Ser146 and degrades MOB1 via the ubiquitin–proteasome system (UPS) in neural cells of SCI. Then, we will discovery a novel monoclonal antibody targeting this site able to inhibit MOB1 phosphorylation and stabilize MOB1 protein，activating downstream LATS/NDR kinase, promoting NSC differentiation and axonal elongation, and ultimately promoting neurological repair after SCI. On the basis of preliminary work, we establish in vivo and in vitro systems to explore the mechanism of MOB1 in promoting endogenous nerve repairment after SCI in mice, and identify the phosphorylation site of Ser146 mediated by GSK3β at MOB1 and its role in vivo, and provide a theoretical basis for drug development for the treatment of SCI in future.