铁蛋白轻链（FTL）基因在阿尔茨海默病发病中的作用及机制研究

阿尔茨海默病（AD）严重影响人类健康，但发病机制未明。近年研究提示，铁沉积诱发氧化应激与Aβ沉积，可能在AD发病中起重要作用。有报道指出，认知功能受损患者杏仁核中铁蛋白轻链（FTL）蛋白表达增高。我们近期工作发现，中度AD小鼠海马中FTL基因在多种细胞中表达，FTL蛋白和Aβ水平与野生型小鼠相比显著升高并呈正相关，提示FTL基因高表达与AD发病相关，可能的机制是通过影响铁沉积、产生ROS、促使Aβ沉积、激活小胶质细胞形成恶性循环。本研究在前期结果基础上，拟结合AD小鼠模型和AD患者脑组织，研究AD不同阶段海马中FTL基因表达变化，并通过FTL基因敲除小鼠及病毒介导的FTL过表达，调控FTL表达量；联合单细胞RNA-seq、免疫染色、Western Blot、ELISA、药理学及行为学等方法，阐明FTL基因在AD发病中的作用及可能机制。本研究有望为AD病理机制提供新思路。

The pathogenesis of Alzheimer's disease (AD) has not yet been fully elucidated. Recent studies have shown that iron deposition may induce oxidative stress and Aβ deposition, which are important mechanisms for the pathogenesis of AD. Studies have reported that the expression level of ferritin light polypeptide (FTL) protein were increased in the amygdala in patients with cognitive impairment. In our previous studies, we found that FTL gene was expressed in different kinds of cells in the hippocampus of mice with moderate AD, and FTL protein and Aβ were significantly increased compared with wild type mice. These results indicates that overexpression of FTL gene is involved with the pathological process of AD. The possible mechanism could be influencing the deposition of iron, inducing ROS production, promoting the deposition of Aβ, and activating microglia, which forms a vicious circle. On the basis of previous results, we will use AD mouse model and postmortem brains of AD patients to explore the FTL gene expression changes in the hippocampus throughout the process of AD and use FTL knock-out hybridization and virus-mediated gene overexpression mouse model to regulate FTL expression. Single-cell RNA-sequencing, immunohistochemical staining, Western blot, ELISA, pharmacological and behavioral studies will be used to find out the possible mechanism of FTL in the pathogenesis of AD. This study will provide new ideas for the pathological mechanism of AD.