非对称性二甲基精氨酸(ADMA)是一种内源性一氧化氮合酶抑制剂，由蛋白质精氨酸甲基转移酶 1(PRMT1)在催化蛋白甲基化的过程中生成，在体内被二甲基精氨酸二甲胺水解酶1(DDAH1)降解，形成一条PRMT1-ADMA-DDAH1代谢轴。ADMA水平异常增高能够导致血管内皮功能失常。研究表明，血管性损伤参与了阿尔茨海默病(AD)的发病进程。我们已经发现，AD细胞模型中ADMA的含量显著升高，但ADMA对AD的影响还不清楚。由此，本项目首先研究AD细胞模型中PRMT1-ADMA-DDAH1代谢轴的动态变化；其次我们将采用添加ADMA、过表达和RNAi干扰技术，研究PRMT1-ADMA-DDAH1代谢轴对AD细胞模型和线虫模型CL2006中Aβ含量和沉积、活性氧水平和动物行为等方面的影响。这些数据将揭示ADMA在AD疾病中的作用机制，为AD的预防与治疗提供新的途径。

Asymmetric dimethylarginine(ADMA), an endogenous inhibitor of nitric oxide synthase, is produced by type I protein-arginine methyl transferase (PRMT1) during the proteolysis of methylated arginine residues on various proteins. ADMA is actively degraded by the intracellular enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1). Thus, PRMT1-ADMA-DDAH1 forms a metabolic axis. The presence of abnormal elevated levels of ADMA is associated with endothelial dysfunction. It has been reported that vascular injury was involved in the pathology of Alzheimer's disease(AD) and we have found that ADMA level was increased in AD cell model, however, it is still unknown whether ADMA plays a role in the development of AD. In order to answer such question, the changes of PRMT1-ADMA-DDAH1 axis in AD cell model will be firstly examined. And then ADMA treatment, overexpression and RNAi techniques will be performed to study the effect of PRMT1-ADMA-DDAH1 axis on Aβ level, deposition, reactive oxygen species and animal behavior in cell and Caenorhabditis elegans (CL2006) models. Our data will reveal the role of ADMA in the pathogenesis of AD and provide novel approach for AD prevention and treatment.