阿尔茨海默症（Alzheimer's disease，AD）是对老年人危害最大的疾病之一, 无治愈药物。具有拟神经生长因子（nerve growth factor, NGF）活性的物质有望用于治疗AD。在前期发现的中药龙胆拟NGF活性新苯甲酸酯及合成的上百个衍生物构效研究的基础上，确定2,3-二羟基苯甲酸十四酯 (命名为ABG-001)为活性先导化合物。细胞实验结果显示ABG-001具有非常显著的拟NGF活性。动物试验结果表明ABG-001具有显著的神经营养和保护作用，能促神经再生。本项目拟应用化学生物学的策略、方法和手段，设计并合成ABG-001的分子探针，发现其靶标，通过RT-PCR、免疫印迹、siRNA等实验进行验证。同时，利用多种现代技术和方法，特别是基因芯片技术，研究ABG-001拟NGF活性的靶标下游的信号通路，阐明其特殊的作用机制，为ABG-001抗AD药物研发提供支持。

Alzheimer's disease is one of the most harmful diseases to old people. There is no drug to cure the disease. Substance possessing nerve growth factor (NGF) mimic activity is promising to treat AD. In our previous study, new benzoates with NGF mimic activity were isolated from a traditional Chinese medicine - Gentiana rigescens Franch. Based on the structure-activity relationship study of more than one hundred benzoate derivatives, tetradecyl 2,3-dihydroxybenzoate (renamed as ABG-001) was decided to be a lead compound. ABG-001 exhibited very significant neuritogenic activity on cell evaluation systems. Results of animal experiments showed that ABG-001 possesses neurotrophic and neuron protective functions. It can promote nerve regeneration. This project intends to apply the chemical biology strategy, design and synthesize molecular probes possessing ABG-001 skeleton and exhibiting equivalent activity as ABG-001. The potential target proteins of ABG-001 will be detected by using these probes. In the meantime, utilize modern techniques and methods, such as gene chip technology, study drown stream signaling pathways of ABG-001 target and the special mechanism of action of ABG-001 should be clarified. This study will provide guidance for anti-AD drug development of ABG-001.