神经免疫和炎症等多种机制参与了帕金森病(PD)中多巴胺能（DA）神经元的退变，它们的分子机制尚不清楚。NOD样受体NLRC5是细胞内模式识别受体家族的一员，对其研究集中于外周免疫反应，但在脑内功能不详。我们发现NLRC5在黑质-纹状体通路中DA神经元、神经胶质细胞内表达，并受毒素MPTP调节。在M1型极化的原代小胶质细胞和A1型极化的原代星形胶质细胞中NLRC5表达上升，提示其可能成为胶质细胞损伤性激活的新标志。用NLRC5敲除（KO）小鼠建立MPTP PD模型，相比对照小鼠，黑质-纹状体通路的损伤得到缓解，胶质细胞的激活减弱；在体外经毒素刺激，原代KO小鼠胶质细胞内促炎分子的表达显著减少，提示NLRC5在PD中调节了神经炎症和神经元退变。本课题将深入探究NLRC5在脑内的功能及在PD中的损伤作用与机制。结果将丰富PD发病中神经免疫与炎症的细胞分子机制，为PD的炎症干预提供新的理论和依据。

Parkinson's disease (PD) is the second most common neurodegenerative disease in the central nervous system (CNS). A variety of mechanisms, including neuroimmune and inflammation, are involved in progressive loss of dopaminergic (DA) neurons in the substantia nigra of the midbrain. Since its cloning in 2010, NOD-like receptor NLRC5 has been focused on its function in the peripheral immune reactions. We found that NLRC5 is highly expressed in the midbrain and the striatum and is present in DA neurons, astrocytes and microglial cells. Furthermore, its expression level is regulated by neurotoxin MPTP. The increased expression of NLRC5 in M1-polarized primary microglia and A1-polarized primary astrocytes suggests that NLRC5 may be a new marker of neurotoxic glial cells. MPTP was used to establish PD models in NLRC5 knockout (KO) mice and control wild-type (WT) mice. We found MPTP caused less severe damage and less glial activation in the nigrostriatal pathway of KO mice, compared to WT mice. After in vitro toxin stimulation, the expression of pro-inflammatory molecules in primary glial cells of KO mice was significantly lower than that of WT mice. In this project, we aimed to clarify the physiological function of NLRC5 in the CNS and the mechanisms involved in the deleterious effect of NLRC5 in PD through the in vitro and in vivo studies. The results will enrich the molecular mechanism of immune and inflammation in PD, and provide a new theoretical and experimental basis for the anti-inflammatory intervention for PD.