The role of miRNA in microglia activation

miRNA 在小胶质细胞激活中的作用

• 批准号: 7511553
• 负责人: THOMAS MOELLER
• 金额: $ 17.06万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7511553
• 关键词: 3' Untranslated Regions; Acute; Animals; Cell surface; Cells; Chronic; Class; Code; Complement; Condition; Crossbreeding; DNA; Data; Development; Evaluation; Fluorescence-Activated Cell Sorting; Functional disorder; Gene Expression Regulation; Genes; Genetic; Goals; Hand; Human; Immune Cell Activation; Immune system; In Vitro; Infarction; Injury; Ischemic Brain Injury; Laboratory Study; Lymphocyte Activation; Maintenance; Malignant Neoplasms; Mammals; Memory; Messenger RNA; MicroRNAs; Microglia; Middle Cerebral Artery Occlusion; Modeling; Molecular; Multiple Sclerosis; Mus; Nerve Degeneration; Neurons; Nucleotides; Numbers; Phenotype; Physiological reperfusion; Physiology; Primates; Process; Proteins; Public Health; Publishing; RNA; Regulation; Reperfusion Therapy; Rest; Role; Signal Transduction; Site; Stroke; Synapses; Testing; Therapeutic Intervention; Translations; Trauma; Untranslated Regions; Vertebrates; central nervous system injury; concept; cytokine; immune function; in vivo; knock-down; macrophage; man; nervous system disorder; neurobehavioral; novel strategies; numb protein; research study

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.

描述（由申请人提供）：小胶质细胞是CNS的常驻巨噬细胞，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CNS病理生理学中的作用，但对控制小胶质细胞活化过程的分子机制了解较少。遗传学的最新进展已经确定了一类新的RNA分子，称为microRNA（miRNA），参与基因调控。miRNA是与mRNA的3'非翻译区（UTR）中的位点互补的约22个核苷酸的单链RNA分子。miRNA与mRNA的退火抑制蛋白质翻译，有时促进mRNA的切割。这种调节为DNA mRNA蛋白质的经典线性概念增加了一层意想不到的复杂性。近两年的研究进展表明，miRNA在调节神经和免疫功能中的重要性。尽管有这些里程碑式的进展，miRNAs在小胶质细胞活化中的功能作用目前尚不清楚。我们现在假设miRNA是小胶质细胞活化过程的一个组成部分，并且在调节下游效应子功能如细胞因子释放中起中心作用。我们建议测试这一假设有以下三个目标：1。获得小胶质细胞中miRNA表达及其激活调节的全面图片。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。该项目的广泛的长期目标是了解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揭示新的方法来治疗与小胶质细胞活化相关的CNS损伤，如中风。该项目的广泛的长期目标是了解miRNAs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构成新的治疗干预与小胶质细胞活化，如创伤，多发性硬化症或中风的CNS损伤的目标。