LXR通路对TC-PTP蛋白调控与抗老年痴呆疾病的应用及机制研究

老年痴呆疾病 (alzheimer's disease, AD)患者认知功能与脑内炎症密切相关，T细胞酪氨酸蛋白磷酸酶 (T-Cell Protein Tyrosine Phosphatase, TC-PTP)是抑制机体内炎症反应的重要磷酸酶，肝X受体 (liver X receptor, LXR)是配体依赖的核转录因子，亦可抑制体内炎症效应。我们在前期实验过程中发现，LXR激动剂可以上调胶质细胞中TC-PTP蛋白，序列比对及双荧光素酶报告基因预测TC-PTP可能是LXR的靶蛋白。此外，我们还发现在老年痴呆疾病患者脑组织内TC-PTP表达降低，且LXR可以TC-PTP活性依赖的方式抑制免疫相关炎症相关因子的表达。为此，我们提出LXR—TC-PTP通路通过对免疫炎症因子的调控，抑制老年痴呆疾病进展的假设。我们期待通过该研究揭示LXR抗老年痴呆新机制，并且为老年痴呆治疗药物设计提供参考。

Inflammation has been attracting great attentions because of its essential roles in the biological and pathological processes of alzheimer's disease (AD), T-Cell Protein Tyrosine Phosphatase (TC-PTP) is an important phosphatase protein that inhibits the production of pro-inflammatory cytokines, and liver X receptor is a ligand activated nuclear transcription factor and is able to alleviate inflammation in vivo. Previously, we found that the LXR ligand induced the expression of TC-PTP in microglia cells and astrocytes, and dual luciferase report assay analysis implied that TC-PTP might be the LXR target protein. Furthermore, the expression of TC-PTP was lower in alzheimer's disease patients in vivo, and abnormal TC-PTP impaired the anti-inflammatory effects of LXR. Therefore, we focus on the inflammatory role of LXR—TC-PTP towards treatment of alzheimer’s disease. We hope that will discover a new target and hypothesis for treatment of alzheimer’s disease.