The role of miRNA in microglia activation

描述（由申请人提供）：小胶质细胞是中枢神经系统的巨噬细胞，与许多急性和慢性神经系统疾病有关，包括多发性硬化症、创伤和中风。虽然许多实验室正在研究活化的小胶质细胞在中枢神经系统病理生理中的作用，但控制小胶质细胞活化过程的分子机制尚不清楚。遗传学的最新进展已经确定了一类新的RNA分子，称为microRNAs (miRNA)，参与基因调控。mirna是约22个核苷酸的单链RNA分子，与mrna的3'非翻译区（UTR）的一个位点互补。miRNA对mRNA的退火抑制蛋白质翻译，有时促进mRNA的切割。这种调控为DNA mRNA蛋白的经典线性概念增加了一层意想不到的复杂性。近两年的快速进展显示了miRNA在调节神经元和免疫功能中的重要性。尽管有这些里程碑式的进展，mirna在小胶质细胞激活中的功能作用目前尚不清楚。我们现在假设mirna是小胶质细胞激活过程的一个组成部分，并在调节下游效应功能（如细胞因子释放）中起中心作用。我们提出以下三个目标来检验这一假设：1。全面了解miRNA在小胶质细胞中的表达及其活化调控。2. 确定特定mirna在小胶质细胞生理学中的作用。3. 确定miR-155在缺血性脑损伤中的作用。该项目的长远目标是了解mirna在小胶质细胞活化中的作用。我们相信，通过我们的实验确定的分子机制可能会为治疗中风等与小胶质细胞激活相关的中枢神经系统损伤提供新的方法。该项目广泛而长期的目标是了解mirna在小胶质细胞活化中的作用。我们相信，通过我们的实验确定的信号转导机制可能成为创伤、多发性硬化症或中风等与小胶质细胞激活相关的中枢神经系统损伤治疗干预的新靶点。

DESCRIPTION (provided by applicant): Microglia, the resident macrophages of the CNS, are implicated in many acute and chronic neurological diseases, including multiple sclerosis, trauma and stroke. While many laboratories are studying the role of activated microglia in CNS pathophysiology, the molecular mechanisms controlling the activation process of microglial are less understood. Recent progress in genetics has identified a new class of RNA molecules called microRNAs (miRNA) involved in gene regulation. miRNAs are single-stranded RNA molecules of ~22 nucleotides complementary to a site in the 3' untranslated region (UTR) of mRNAs. The annealing of the miRNA to the mRNA inhibits protein translation and sometimes facilitates cleavage of the mRNA. This regulation adds an unexpected layer of complexity to the classic linear concept of DNA mRNA protein. Fast paced progress in the last two years showed the importance of miRNA in regulating neuronal and immune functions. Despite these landmark advances, the functional role of miRNAs in microglial activation is currently unknown. We now hypothesize that miRNAs are an integral part of the microglial activation process and central in regulating downstream effector functions such as cytokine release. We propose to test this hypothesis with the following three aims: 1. Obtain a comprehensive picture of miRNA expression in microglial cells and their regulation by activation. 2. Identify the role of specific miRNAs in microglial physiology. 3. Identify the role of miR-155 in ischemic brain injury .The broad, long-term goal of this project is to understand the role of miRNAs in microglial cell activation. We believe that the molecular mechanisms identified through our experiments may reveal new approaches for therapeutic intervention in CNS injuries associated with microglial activation such as stroke. PUBLIC HEALTH RELEVANCE The broad, long-term goal of this project is to understand the role of miRNAs in the activation of microglial cells. We believe that the signal transduction mechanisms identified through our experiments may constitute new targets for therapeutic intervention in CNS injuries associated with microglial activation such as trauma, multiple sclerosis or stroke.