Oligodendrocyte ontogeny and differentiation

少突胶质细胞个体发育和分化

基本信息

批准号：
7596207
负责人：
ELISA M BARBARESE
金额：
$ 32.38万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7596207
关键词：
3&apos Untranslated Regions Affect Animals Astrocytes Axon Binding Proteins Brain CPE-binding protein Cell Fractionation Cell Nucleus Cell physiology Cells Cessation of life Complementary DNA Cytoskeleton Differentiated Gene Disease Elements Environment Failure Gene Proteins Genetic Translation Goals Green Fluorescent Proteins Growth Heterogeneous-Nuclear Ribonucleoproteins Human Indium Life Membrane Messenger RNA Methods Monitor Multiple Sclerosis Myelin Myelin Basic Proteins Neural Conduction Neurons Oligodendroglia Pathologic Pathway interactions Patients Pharmaceutical Preparations Phenotype Play Polyadenylation Process Protein Binding Protein Biosynthesis Proteins RNA Interference RNA-Binding Proteins Radiation Regulation Regulatory Element Research Response Elements Role Series Signal Transduction Site Spinal Cord Symptoms System Techniques Translating Translations Virus Diseases Walking analytical method cell type deletion analysis in vivo knock-down myelination neuronal cell body overexpression premature protein expression protein protein interaction repaired translation assay tumor

项目摘要

DESCRIPTION (provided by applicant): The major function of the oligodendrocyte in the CNS is to produce myelin that envelops axons and allows fast saltatory conduction of nerve impulses. Our long-term goal is to elucidate the process of myelination and its regulation. Since myelin basic protein (MBP) is a major and essential component of myelin we are focused on analyzing the mechanisms that control its expression. MBP is synthesized at its site of assembly in myelin. This is accomplished by transport of its mRNA from the nucleus to the cell body, and further down the cell processes and into myelin where it is anchored and translated. Our aims are to identify the elements in MBP mRNA that regulate its translation, the proteins that bind to these elements and their mode of action, and characterize the sites of MBP mRNA translation and the local factors that are necessary to initiate it. Failure to achieve full remyelination in the presence of adequate number of premyelinating oligodendrocytes in diseases such as multiple sclerosis may be due to the lack of receptivity on the part of the oligodendrocyte, lack of myelination signals on the part of the neuron, or to inhibiting conditions for myelination created by other cell types such as astrocytes. The latter conditions appear to be at play in multiple sclerosis and may have a direct negative effect on MBP expression. In order to accomplish the proposed aims the effects of deletion of translation regulatory elements in MBP mRNA, and knockdown of their specific RNA binding proteins will be assessed in an in vivo translation assay in cultured oligodendrocytes, and the characterization of protein-protein interactions by biophysical methods, and immnunological analysis of translation sites will be performed in cultured oligodendrocytes and in myelin fractions. Several diseases, such as multiple sclerosis, viral infections, or post-radiation symptom exist in humans that are due to the loss of myelin in the brain and the spinal cord. Patients have difficulty walking or doing daily chores. Myelin is a membrane that envelops the axon which is the part of the neuron responsible for nerve conduction. Our research focuses on finding out how myelin is made and how it can be repaired, possibly by the use of pharmacological drugs, so that patients could regain the ability to participate in normal life activities.

描述（由申请人提供）：中枢神经系统中少突胶质细胞的主要功能是产生髓磷脂，该髓磷脂包裹轴突并允许快速盐水传导神经冲动。我们的长期目标是阐明髓鞘及其调节的过程。由于髓磷脂碱性蛋白（MBP）是髓磷脂的主要组成部分，因此我们专注于分析控制其表达的机制。 MBP在其在髓磷脂中的组装部位合成。这是通过将其mRNA从细胞核转移到细胞体的转运，然后进一步沿细胞过程和髓磷脂的降低。我们的目的是确定调节其翻译的MBP mRNA中的元素，与这些元素结合的蛋白质及其作用方式，并表征MBP mRNA翻译的位点以及启动它所需的局部因素。在存在足够数量的疾病中的少突胶质细胞（例如多发性硬化症）中，无法实现完全的再髓，可能是由于缺乏少突胶质细胞的接受性，缺乏髓鞘形成信号，而神经元的一部分或抑制由其他细胞构成其他细胞类型的骨髓质量抑制诸如其他细胞型肌电蛋白质的疾病。后一种情况似乎在多发性硬化症中发挥作用，可能对MBP表达产生直接负面影响。为了完成提议的目标，将在MBP mRNA中删除翻译调节元件的删除，并且将在培养的少突胶质细胞中的体内翻译测定中评估其特定RNA结合蛋白的敲低，并在体内翻译测定中进行评估，并通过生物物质学分析的纯种方法来表现蛋白质 - 蛋白质相互作用。和髓鞘的分数。人类中存在几种疾病，例如多发性硬化症，病毒感染或放射后症状，这是由于大脑和脊髓中髓磷脂丧失所致。患者难以步行或每天做家务。髓磷脂是一种包裹轴突的膜，轴突是负责神经传导的神经元的一部分。我们的研究重点是找出可能通过使用药物药物对髓磷脂的生产方式以及如何修复，以便患者可以恢复参加正常生活活动的能力。