Dyrk1b促进STAT3的磷酸化在星形胶质细胞炎症激活所致神经损伤中的作用机制研究

Inflammatory activation of astrocytes promotes the development of nerve injury in a variety of central nervous system diseases. Serine phosphorylation at position 727 of STAT3 plays an important role in the activation of astrocytes, but its regulatory mechanism is unclear. In the previous study, the research team found that Dyrk1b can bind to STAT3 and promote the phosphorylation of serine at position 727. It is suggested that Dyrk1b promotes serine phosphorylation at position 727 of STAT3 in astrocytes, promote the activation of inflammatory cells and induce the activation of cells. The scientific hypothesis of neuronal damage. In view of this, this project intends to clarify that Dyrk1b binds to STAT3 in astrocyte inflammatory activation model, elucidating the promoting effect of Dyrk1b on serine phosphorylation at position 727 of STAT3, and analyzing the above regulation on astrocyte inflammatory activation and Its role in the induction of neuronal damage; finally in the animal type to analyze the role of Dyrk1b-regulated STAT3 phosphorylation in astrocytes in brain inflammation and neuropathy. The results of this project will provide a basis for elucidating the molecular mechanism of astrocyte STAT3 phosphorylation and provide a target for the treatment of various diseases of the central nervous system.

星形胶质细胞炎症激活促进多种中枢神经系统疾病中神经损伤的发生，STAT3的727号位丝氨酸磷酸化在星形胶质细胞的炎症激活中有重要作用，但是其调节机制不清楚。课题组前期研究发现Dyrk1b可与STAT3结合，促进727号位丝氨酸的磷酸化，据此提出在星形胶质细胞中Dyrk1b可促进STAT3的727号位丝氨酸磷酸化，促进细胞的炎症激活及其导致的神经元损伤的科研假说。鉴于此，本项目拟在星形胶质细胞炎症激活模型中明确Dyrk1b可与STAT3结合，阐明Dyrk1b对STAT3的727号位丝氨酸磷酸化的促进作用，分析上述调节对星形胶质细胞炎症激活及其诱导的神经元损伤的作用；最后在动物模型中分析干预星形胶质细胞中Dyrk1b调节的STAT3磷酸化在脑炎症反应及神经病变中的作用。本项目研究结果将为阐明星形胶质细胞STAT3磷酸化的分子机制提供基础，为寻找中枢神经系统多种疾病的治疗方法提供靶点。

星形胶质细胞炎症激活促进多种中枢神经系统疾病中神经损伤的发生，STAT3的727号位丝氨酸磷酸化在星形胶质细胞的炎症激活中有重要作用，但是其调节机制不清楚。课题组前期研究发现Dyrk1b可与STAT3结合，促进727号位丝氨酸的磷酸化，据此提出在星形胶质细胞中Dyrk1b可促进STAT3的727号位丝氨酸磷酸化，促进细胞的炎症激活及其导致的神经元损伤的科研假说。鉴于此，本项目拟在星形胶质细胞炎症激活模型中明确Dyrk1b可与STAT3结合，阐明Dyrk1b对STAT3的727号位丝氨酸磷酸化的促进作用，分析上述调节对星形胶质细胞炎症激活及其诱导的神经元损伤的作用；最后在动物模型中分析干预星形胶质细胞中Dyrk1b调节的STAT3磷酸化在脑炎症反应及神经病变中的作用。本项目研究结果将为阐明星形胶质细胞STAT3磷酸化的分子机制提供基础，为寻找中枢神经系统多种疾病的治疗方法提供靶点。

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