阿尔茨海默病（AD）是一种神经退行性疾病，神经炎症在AD的发病机制中扮演重要角色。NgR是神经生长抑制分子Nogo-66的受体，小胶质细胞的Nogo-66/NgR通路介导了神经炎症， 但Nogo-66/NgR通路介导的神经炎症是否参与AD的发病机制，国内外尚无相关报道。所以，本课题将利用分子生物学、细胞生物学和转基因动物等技术，从分子、细胞和整体动物多层面，探讨小胶质细胞Nogo-66/NgR通路介导的神经炎症在AD发病机制中的作用， 内容包括（1）Nogo-66/NgR通路介导小胶质细胞对Aβ的粘附、迁移、吞噬和降解作用；（2）Nogo-66/NgR通路介导的炎症环境对神经元生成Aβ、tau蛋白的磷酸化、Aβ聚集的影响；（3）Nogo-66/NgR通路阻断后对转基因AD小鼠的Aβ沉积、空间记忆的影响。本课题的完成将为以后针对Nogo-66/NgR通路为靶点的AD药物开发提供新的思路。

Alzheimer's disease (AD) is a common neurodegenerative disease with neuropathological hallmarks of intracellular neurofibrillary tangles and extracellular senile plaque composed primarily of amyloid β-peptides (Aβ). Neuroinflammation has been highlighted as one possible key contributing factor to AD. The classic hallmarks of neuroinflammation, such as activated microglia, activated astrocyte and increased cytokine expression, are all observed in the tissue of AD patients and transgenic AD mice. Nogo receptor (NgR) is the receptor of myelin-associated inhibitor Nogo-66. NgR expressed on the neuron participates not only in arresting neurite outgrowth but also in Aβ pathology. NgR also expresses on the microglia and Nogo-66/NgR signaling pathway mediates neuroinflammation via microglia, but the role of neuroinflammation mediated by Nogo-66/NgR in the AD pathogenesis remains unclear. Therefore, this project will explore the role of neuroinflammation mediated by Nogo-66/NgR signaling pathway in the AD pathogenesis by use of molecular technology, cellular technology and Alzheimer's transgenic mice, etc. The research contents about this project will include three parts: (1) The role of Nogo-66/NgR pathway on the mediating microglia adhesion, migration, Aβ uptake and Aβ degradation; (2) The influences of neuroinflammation mediated by Nogo-66/NgR pathway on the Aβ production, tau hyperphosphorylation and Aβ aggregation; (3) The effects of blockade of Nogo-66/NgR pathway on the Aβ plaque and spatial memory in Alzheimer's transgenic mice. This study will help to clarify the relationship between Nogo-66/NgR, microglia, neuroinflammation and AD and highlight the role of neuroinflammation in Alzheimer's disease. The Nogo-66/NgR will provide a novel site for modifying the course of AD and become to be potential target for drug development in treatment AD.