DEVELOPMENTAL REGULATION OF THE NERVE GROWTH FACTOR RECEPTOR GENE

神经生长因子受体基因的发育调控

• 批准号: 6572330
• 负责人: MOSES VICTOR CHAO
• 金额: $ 8.64万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6572330
• 关键词: SDS polyacrylamide gel electrophoresis; apoptosis; cell differentiation; cell line; choline acetyltransferase; cysteine endopeptidases; developmental neurobiology; enzyme activity; gene expression; genetic regulation; growth factor receptors; immunocytochemistry; immunoprecipitation; laboratory mouse; laboratory rabbit; laboratory rat; molecular cloning; neurotrophic factors; nuclear factor kappa beta; nucleic acid sequence; oligodendroglia; prosencephalon; protein tyrosine kinase; receptor expression; tissue /cell culture

Neurotrophins are secreted proteins which influence the proliferation, differentiation, survival and death of neuronal and non-neuronal cells during vertebrate development. It is likely that the information concerning the mechanism of action of neurotrophin receptors will lead to a greater understanding of how the multiple actions and specificity are encoded in these trophic factors. NGF, BDNF, NT-3 and NT-4 exert their actions through two types of receptors, the trk family of tyrosine kinase receptors and a unique receptor termed p75. While the effects of NGF upon neuronal cell survival and differentiation are well documented, recent evidence indicates that NGF may be involved in promoting programmed cell death in the nervous system. The purpose of this subproject is to elucidate the mechanism by which neurotrophins act through the p75 and trk receptors in regulating apoptosis. Downstream signaling pathways involving activation and time course of the stress-activated kinase (c-jun kinase) activity and Nfkappab transcription activity will be assessed. This investigation will yield new insights which may lead to the development of strategies to counter several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Alzheimer's disease and multiple sclerosis.

神经营养因子是一种能影响细胞增殖的分泌性蛋白质， 神经细胞和非神经细胞的分化、存活和死亡 在脊椎动物的发育过程中。很可能这些信息 关于神经营养素受体的作用机制将导致 更好地理解多重行动和特殊性是如何 编码在这些营养因子中。神经生长因子、脑源性神经营养因子、NT-3和NT-4发挥其功能 通过两种受体发挥作用，即酪氨酸激酶trk家族 受体和一种名为p75的独特受体。而神经生长因子对血管生成的影响 神经细胞的存活和分化是有充分证据的，最近 有证据表明，NGF可能参与促进程序化细胞 神经系统死亡。这个子项目的目的是 阐明神经营养因子通过p75和trk的作用机制。 调节细胞凋亡的受体。下游信号通路涉及 应激激活激酶(c-jun激酶)的激活和时程 将评估活性和Nfkappab转录活性。这 调查将产生新的见解，这可能导致 对抗几种神经退行性疾病的策略，例如 肌萎缩侧索硬化症、阿尔茨海默病和多发性硬化症。