小胶质细胞激活广泛存在于神经系统退行性疾病中，在病理过程的发生和发展中有着重要功能。然而，神经退行性病变诱导的小胶质细胞激活的调控机制及其病理作用仍有待全面深入阐明。申请人课题组在最新研究中，利用创伤性损伤引发的视神经退行性病变为模型，开始揭示小胶质细胞来源的TGFbeta信号在其自身激活及神经损伤修复中关键性的调控功能。基于已有工作基础，本申请项目将着重探索TGFbeta在小胶质细胞激活中的调控机制及病理作用，具体研究将围绕以下三个方面展开：1、TGFbeta在神经退行性病变诱导小胶质细胞激活中的调控功能；2、调控小胶质细胞TGFbeta表达的分子机制；3、小胶质细胞来源TGFbeta在神经损伤修复中的病理作用及机制。本申请项目研究成果将有力推动对于小胶质细胞参与神经系统疾病特别是神经退行性疾病病理过程的深入理解，同时为通过靶向小胶质细胞治疗神经系统疾病的药物研发提供新的切入点。

Microglial activation has been widely observed in many neurodegenerative disorders, and has been known for exerting important roles in the onset and progression of these disease conditions. However, the mechanism, as well as the pathophysiological function, underlying the microglial activation in neurodegeneration remains to be fully understood. Our research group has recently discovered that in the model of neurodegeneration induced by traumatic optic nerve injury, TGFbeta derived from microglia has a key role in regulating the activation of themselves and also the progress of neural repair. Based on our existing results, this project is aimed to understand function and regulatory mechanism of TGFbeta in the microglial activation during neurodegeneration. The research work will be carried out following the specific aims: (1) Function of TGFbeta in the microglial activation during neurodegenerative process; (2) Regulatory mechanism of microglial TGFbeta signal; (3) Pathophysiological function and mechanism of microglial TGFbeta signal in neural repair. This research project will significantly advance our knowledge on the microglial functions in neurodegeneration, and at the same time, provide a novel entry point of targeting the microglial activation for treatment of neurodegenerative disease.