TROY及其信号分子在多发性硬化症中的作用及机制研究

多发性硬化症是最常见的神经免疫性疾病，以中枢神经系统白质炎性脱髓鞘病变为主要特点，小胶质细胞在其病变过程中扮演重要作用。目前，对其尚缺乏有效治疗手段。改善多发性硬化症诊疗现状需要大力加强相关基础研究。TROY受体在脑中有广泛表达，但它在小胶质细胞中所起的作用还很不清楚。我们在预实验研究中发现：TROY在脑中星形与小胶质细胞中有表达，在实验性脑炎小鼠脑小胶质细胞中表达水平显著提高；LPS刺激体外培养的小胶质细胞可以显著提高其中TROY表达；TROY还可以与多种炎症相关基因结合。本项目拟在已有工作基础上，深入发掘TROY及其信号通路在多发性硬化中的生物学作用，阐明介导这些效应的细胞和分子机制；探讨通过干预TROY及其信号通路改善多发性硬化症脑病过程的可能性。我们期望，这项研究能深化现有对TROY受体及其信号转导在多发性硬化症病变中作用的认识，并为潜在的临床应用提供理论和实践支持。

Multiple sclerosis (MS) is the most common type of the neuroimmunological diseases which is characterizaed by inflammatory demyelination of white matter in CNS. Microglia play key roles in pathologic process of MS. However,the effective therapy to control the MS is limited. In order to promote the novel therapeutic measurements,it need to strengthen the basic study on this disease.It has been reported that TROY receptor is broadly expressed in the brain.But the roles of which in the microglia remain elusive.In our preliminary data,we found that TROY was expressed in astrocytes and microglia of brain.The level of TROY in microglia of experimental autoimmune encephalomyelitis (EAE) models was significant higher than that in the control.The TROY expression was up-regulated by LPS stimulation in cultured microglia in vitro.Additionally,we also found that TROY interacted with several proteins, which had been reported as inflammation-related genes. Based on our interesting premilinary data, we plan to further detect the roles of TROY and its downstream signaling in the MS.To clarify the mechanism underlying these effects. To search the possibility to improve pathologic process of MS through intervene in TROY and the downstream signaling. We hope that our plan should not only deepen insight into the roles of TROY and its signaling in the MS but also provide clued to the potential clinical use.