帕金森病遗传与环境因素对小胶质细胞的激活及机制

项目名称： 帕金森病遗传与环境因素对小胶质细胞的激活及机制

项目编号： No.31330030

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 神经、认识与心理学

项目作者： 王光辉

作者单位： 苏州大学

项目金额： 307万元

中文摘要： 在帕金森病（PD）患者，无论是遗传性和散发性，脑中均有胶质细胞的激活和炎症因子表达的增加，但触发小胶质细胞激活炎症反应的分子机制以及遗传与环境如何互作对其影响依然不明。我们在以往研究中发现，遗传因素park13基因产物（OMI）和环境因素鱼藤酮均可通过MAPK通路激活小胶质细胞，引起炎症因子的产生。本项目拟运用生物化学、细胞生物学和动物模型，研究环境因素（MPTP及鱼藤酮）和遗传因素（OMI）对MAPK及NF-κB信号通路的作用及其激活小胶质细胞机制，观察MAPK及NF-κB与PD炎症反应在模型动物损伤脑区的关联性；并研究小胶质细胞-星形胶质细胞在炎症反应中的作用及其对多巴胺能神经元死亡的影响并，探讨神经元-胶质细胞互作在PD发生中的作用。通过项目实施，阐明PD炎症发生中小胶质细胞激活与MAPK-NF-κB信号通路的调节机制。

中文关键词： 小胶质细胞;神经退行性疾病;帕金森病;神经系统疾病;神经炎症

英文摘要： The activation of glial cells and increased expressions of inflammatory factors are presented in Parkinson disease brains of both heriditary and sparadic patients. However, it keeps largely unknown by which the inflammatory reaction is triggered and how genetic and environmental factors. We recently found that the genetic factor OMI, a gene product of park13, and environmental factor totenone regulate MAPK pathway to activate microglia. We plan to investigate the role of the environment factors (MPTP and rotenone) and the genetic factors (PD gene product OMI) in the regulation of MAPK and NF-κB pathways using biochemical, cellular biological methods, as well as animal models. We will examine if the activations of MAPK and NF-κB pathways are specifically presented in the damaged regions in animal brains and if there are correlations between them. We will also investigate the role of astrocyte and microglia in inflammation and their contributions to dopaminergic neuronal cell death. We expect to elucidate by which mechanism MAPK and NF-κB pathways and microglia are acivated in the inflammations in PD.

英文关键词： microglia;neurodegenerative disease;Parkinson disease;neurological disease;neuroinflammation