TREM2基因在晚发型AD（LOAD）中介导Aβ吞噬与炎症调节的机制研究

项目名称： TREM2基因在晚发型AD（LOAD）中介导Aβ吞噬与炎症调节的机制研究

项目编号： No.81460183

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 石胜良

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： 晚发型阿尔茨海默病（late-onset Alzheimer's disease, LOAD)是阿尔茨海默病的重要分型，其发病的核心与基础是细胞外β-淀粉样蛋白（Aβ)异常集聚以及由其引发的神经细胞毒性作用。研究表明TREM2基因与LOAD发病有关，其在介导小胶质细胞Aβ吞噬以及调节中枢神经炎症中有重要作用，然而，迄今其确切的机制尚未明了。本研究将通过建立敲除与过表达TREM2基因的AD细胞模型以及敲除TREM2基因的动物模型，采用慢病毒载体转染、RT-PCR、Western blot、免疫组化、行为学测试等手段从分子、细胞、组织以及整体水平等多层次研究TREM2基因与Aβ吞噬及中枢炎症的关系；探讨TREM2基因与TLRS通路在LOAD 介导Aβ吞噬及调节神经炎症的作用及调控机制，为揭示TREM2基因在LOAD的作用机制奠定一定的理论基础，为靶向治疗LOAD提供新的靶点。

中文关键词： 阿尔茨海默病；晚发型阿尔茨海默病；TREM2基因；Aβ吞噬；炎症调控

英文摘要： Abnormal accumulation and neuronal toxicity of extracellular β-amyloid (Aβ) are the core and basic pathological features for AD and late-onset Alzheimer's disease (LOAD).Many studies have shown that Triggering Receptor Expressed on Myeloid cells 2 (TREM2 gene) is associated with LOAD. TREM2 can mediate the Aβ phagocytosis of microglia and inflammatory regulation processes by the central nervous system(CNS). However, its exact mechanism is not yet clear. Our research will study both TREM2 gene knockout in AD cell and animal models as well as TREM2 gene overexpression in AD cell model.The lentiviral vector-transfection, real-time PCR, Western blot, immunohistochemistry and behavioral test from the different levels of organization as molecules, cells, tissues and animals' level will be studied to investigate the relationships between TREM2 gene and Aβ phagocytosis as well as the inflammation of the central nervous system. Moreover, we will explore the functions and regulation mechanisms of TREM2 gene and TLRS pathways in mediating Aβ phagocytosis and the nervous inflammation in LOAD.We aim to lay a theoretical foundation for the function of TREM2 gene and develop a new therapeutic target for LOAD in the future.

英文关键词： Alzheimer's disease;AD;late-onset Alzheimer’s disease;LOAD;TREM2 gene;Aβ phagocytosis;inflammation regulation