GPCR/β-arrestin 信号转导是目前神经精神疾病研究和药物研发的热点，但是其对于神经元之外胶质细胞功能（尤其是神经炎症调节）的影响尚未被揭示。本项目拟在前期发现β-arrestin 2敲除加重帕金森病（PD）模型小鼠DA神经元丢失和星形胶质细胞活化，多巴胺D2受体（D2R）激动剂通过β-arrestin 2依赖的方式抑制星形胶质细胞炎症反应的基础上，应用星形胶质细胞D2R条件敲除和β-arrestin 2条件敲除小鼠研究星形胶质细胞D2R/β-arrestin 2介导的非经典通路在PD发生中的作用，揭示β-arrestin偏爱型配基对PD的实验治疗学意义；阐明D2R/β-arrestin 2通路对星形胶质细胞NLRP3炎症小体活化和非炎症小体途径神经炎症的调节及机制。预期研究成果不仅有助于深化对PD神经炎症学说的认识，也为研发β-arrestin偏爱型激动剂治疗PD积累学术基础。

GPCR/β-arrestin signaling exerts important roles in neuropsychiatric disorders and has been regarded as the key target for drug development. However, the effect of GPCR/β-arrestin on glial function, especially in modulating neuroinflammation remains unclear. Our previous study revealed that β-arrestin 2 knockout aggravated DA neuron degeneration and astrocyte inflammation in Parkinson's disease (PD) model. D2R agonist inhibited neuroinflammation in a β-arrestin 2-dependent manner. This project thus is designed to investigate the role of D2R/β-arrestin 2 signaling in the pathogenesis of PD with Drd2/β-arrestin 2 conditional knockout mice, and discover the experimental therapeutical value of β-arrestin 2 biased ligands in PD. Furthermore, we will clarify the detailed mechanism for astrocytic D2R/β-arrestin 2 signaling in regulating NLRP3 inflammasome-mediated neuroinflammation. This work will give us a novel insight into the etiology of PD and is beneficial to a breakthrough in PD therapeutics.