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Neuronal Cell Cycle and Survival

神经细胞周期和存活

基本信息

批准号：
8387997
负责人：
Nicholas E Baker
金额：
$ 35.7万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8387997
关键词：
Actins Address Adult Affect Alzheimer&apos s Disease Apoptosis Architecture Autophagocytosis Axon Axonal Transport Cell Cycle Cell Cycle Progression Cell Death Cell Nucleus Cell Proliferation Cell Survival Cell division Cells Cellular Structures Centrosome Cessation of life Characteristics Charcot-Marie-Tooth Disease Cyclin A Cytokinesis Cytoskeleton Daughter Defect Down-Regulation Drosophila genus Drosophila melanogaster Event Eye Fishes Frontotemporal Dementia Gene Mutation Genes Genetic Genetic Screening Genetic Techniques Hereditary Spastic Paraplegia Huntington Disease Lead Link Location Maintenance Malignant Neoplasms Measures Microtubules Mitosis Mitotic Molecular Genetics Motor Mutation Necrosis Nerve Degeneration Nervous system structure Neurodegenerative Disorders Neurons Nuclear Parkinson Disease Pathway interactions Photoreceptors Positioning Attribute Primary Lateral Sclerosis Proliferating Proteins Research Rest Retina Retinal Retinal Degeneration Retinoblastoma Role Route S Phase Signal Pathway Spinocerebellar Ataxia Type 5 Stem cells Stroke Structure Syndrome System Time Transgenic Organisms Viral Encephalitis Withdrawal base design fly genetic manipulation mutant neuron loss neuronal survival novel novel strategies nuclear division prevent retinal neuron trafficking

项目摘要

DESCRIPTION (provided by applicant): The research addresses how photoreceptor neurons withdraw permanently from the cell cycle, and the relationships of cell cycle withdrawal to both neural degeneration and to cancer. A new hypothesis is proposed that relates cell cycle withdrawal to the axonal structure of photoreceptor neurons, and to their survival. The eye of the fruit fly Drosophila melanogaster will be used to evaluate this new hypothesis, and to identify specific aspects of cell cycle progression, or of postmitotic structure, that trigger neuronal loss, as well as to search for novel, unknown genes that influence these events. These objectives will be achieved by using transgenic fruit flies and molecular genetic techniques to target RNAs and proteins to specific subsets of photoreceptor cells in a conditional manner. In this way, components of the cell cycle, cytoskeleton, and multiple cell death pathways will be manipulated to determine their effects on the maintenance of cell cycle quiescence, on the structure of photoreceptor cells and especially their axons, and on the cell-autonomous and non-autonomous mechanisms of photoreceptor cell survival. The information obtained in this study is expected to guide approaches to reduce proliferation of retinoblastoma, to minimize neuronal loss in some retinal degeneration, and possibly to reduce neuronal loss in other neurodegenerative conditions such as Alzheimer's Disease, Amylotrophic Lateral Sclerosis, Huntington's Disease, Charcot-Marie Tooth Disease, hereditary spastic paraplegia SPG10, Spinocerebellar Ataxia type 5, Fronto-temporal Dementia, certain viral encephalitis syndromes, Parkinson's Disease, and stroke.

描述（由申请人提供）：该研究解决了感光神经元如何从细胞周期中永久退出，以及细胞周期退出与神经变性和癌症的关系。提出了一个新的假说，涉及细胞周期的撤回感光神经元的轴突结构，并对他们的生存。果蝇的眼睛将被用来评估这一新的假设，并确定细胞周期进程的具体方面，或有丝分裂后的结构，触发神经元的损失，以及寻找新的，未知的基因，影响这些事件。这些目标将通过使用转基因果蝇和分子遗传技术以有条件的方式将RNA和蛋白质靶向特定的感光细胞亚群来实现。以这种方式，细胞周期，细胞骨架和多个细胞死亡途径的组件将被操纵，以确定它们对维持细胞周期静止，感光细胞的结构，特别是它们的轴突，以及感光细胞存活的细胞自主和非自主机制的影响。本研究中获得的信息有望指导减少视网膜母细胞瘤增殖的方法，以使某些视网膜变性中的神经元损失最小化，并可能减少其他神经变性病症中的神经元损失，所述其他神经变性病症例如阿尔茨海默氏病、肌萎缩性侧索硬化症、亨廷顿氏病、夏科-马里-图思病、遗传性痉挛性截瘫SPG 10、脊髓小脑性共济失调5型、额颞痴呆、某些病毒性脑炎综合症、帕金森病和中风。