C-JUN DEPENDENT MEDIATIVE GENES IN NEURONAL APOPTOSIS

神经元凋亡中的 C-JUN 依赖性中介基因

• 批准号: 6330378
• 负责人: LUFEN L CHANG
• 金额: $ 3.48万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6330378
• 关键词: PC12 cells; animal genetic material tag; apoptosis; cerebral ischemia /hypoxia; developmental genetics; gene induction /repression; laboratory mouse; laboratory rat; neurogenetics; neurons; oncoproteins; reperfusion; transcription factor

Apoptosis, or programmed cell death is a fundamentally biological process that is required to maintain the integrity and homeostasis of multicellular organism. Inappropriate apoptosis has been associated with many of the most intractable of human diseases, including neurodegenerative disorders and cancer. In an age-related conditions, such as Alzheimer's disease and stroke, there is an increase in an neuronal cell death. A cascade of gene expression is essential to effect neuronal apoptosis. The transcription factor c-Jun is one of the earliest and most consistent marker for neurons that response to neuronal injury and neurodegenerative disorders. Overexpression of c- Jun can trigger apoptosis in sympathetic neurons. Antagonization of c- Jun activity by overexpression of transactivation-defective c-Jun mutants prevents them against nerve growth factor (NGF) withdrawal- induced death. It appears that c-Jun might cause neuronal cell death by initiating the transcription of downstream target genes whose gene products are executors or triggers of the cell death program. However, c-Jun downstream target gene(s) that effect neural apoptosis are largely unknown. The primary goal of this proposal is to directed toward identifying Jun target genes and toward dissecting the mechanism by which is c-Jun is triggering apoptosis.

细胞凋亡或程序性细胞死亡是一种基本的生物学现象 维持完整性和稳态所需的过程 多细胞生物。 不适当的细胞凋亡相关 与许多最难治的人类疾病有关，包括 神经退行性疾病和癌症。 在与年龄相关的条件下， 例如阿尔茨海默病和中风， 神经元细胞死亡。 基因表达级联对于 影响神经细胞凋亡。 转录因子 c-Jun 是其中之一 最早和最一致的神经元响应标记 神经元损伤和神经退行性疾病。 c-的过度表达 Jun可以引发交感神经元凋亡。拮抗c- 通过反式激活缺陷的 c-Jun 过度表达来实现 Jun 活性 突变体阻止它们抵抗神经生长因子（NGF）的戒断- 诱发死亡。 c-Jun 似乎可能导致神经元细胞死亡 通过启动下游靶基因的转录，其基因 产品是细胞死亡程序的执行者或触发者。 然而， 影响神经细胞凋亡的 c-Jun 下游靶基因主要是 未知。 该提案的主要目标是 识别 Jun 目标基因并通过以下方式剖析其机制 这是c-Jun正在触发细胞凋亡。