神经元限制性沉默因子NRSF对小胶质细胞激活的调节作用及其机制研究

帕金森病（Parkinson’s disease, PD）是第二大神经系统退行性疾病，病理机制非常复杂。利用离体和在体的PD模型，我们的研究发现神经元限制性沉默因子（NRSF）参与了PD的发病，但它在小胶质细胞激活中的作用尚不清楚。小胶质细胞的激活与PD的病理过程关系密切，激活的小胶质细胞被分为促炎的M1型和抗炎的M2型，M1型小胶质细胞分泌的神经毒素和促炎因子促进了炎症反应和神经元死亡；而M2型小胶质细胞主要发挥清除病原和抗炎作用。我们的前期工作显示小胶质细胞在M1型和M2型刺激下，NRSF的表达水平分别得到了上调和下调，提示NRSF在小胶质细胞的激活中可能起到负反馈的作用。本项目拟在M1和M2型小胶质细胞中，探索NRSF对小胶质细胞激活的调节作用及其机制，为通过调节小胶质细胞的激活状态治疗PD提供新的实验依据。

Parkinson’s disease (PD) is the second largest neurodegenerative disease. The pathogenesis of PD is complex. Our previous studies show that neuron restrictive silencer factor (NRSF) is involved in both in vitro and in vivo PD models; however, the functions of NRSF in microglia activation are unclear. Activation of microglia is closely related to the progress of PD. Activated microglia comprises pro-inflammatory (M1) and anti-inflammatory (M2) microglia. M1 microglia is associated with the production of neurotoxins and proinflammatory cytokines, which promotes inflammatory response and neuronal death; M2 microglia is associated with eliminating pathogens and anti-inflammatory function. Our previous work has found under the specific M1 or M2 stimulations, NRSF protein levels are upregulated and downregulated respectively, which indicates that NRSF plays as a negative regulator in microglia activation. In this project, we will further investigate the roles and mechanism of NRSF in the two microglia activation pathways, modulating microglia activation states might be a potential therapeutic approach to PD.