Neuronal Cell Cycle and Survival

描述(申请人提供)：这项研究解决了光感受器神经元如何永久退出细胞周期，以及细胞周期退出与神经退化和癌症的关系。提出了一种新的假说，认为细胞周期退出与光感受器神经元的轴突结构及其存活率有关。果蝇黑腹果蝇的眼睛将被用来评估这一新假说，并识别触发神经元丢失的细胞周期进程或有丝分裂后结构的特定方面，以及寻找影响这些事件的新的未知基因。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光感受器细胞亚群来实现。通过这种方式，细胞周期、细胞骨架和多个细胞死亡途径的组成部分将被操纵，以确定它们对维持细胞周期静止的影响，对光感受器细胞的结构，特别是对它们的轴突的影响，以及对光感受器细胞生存的细胞自主和非自主机制的影响。这项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，最大限度地减少某些视网膜变性中的神经元丢失，并可能减少其他神经退行性疾病中的神经元丢失，如阿尔茨海默病、肌萎缩性侧索硬化症、亨廷顿病、夏科特-玛丽-牙病、遗传性痉挛性截瘫SPG10、脊髓小脑性共济失调5型、额颞部痴呆、某些病毒性脑炎综合征、帕金森病和中风。

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.