REGULATION AND PROCESSING OF AMYLOID PRECURSOR PROTEIN GENES AND GENE PRODUCTS

淀粉样前体蛋白基因和基因产物的调控和加工

• 批准号: 2565704
• 负责人: J W KUSIAK
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2565704
• 关键词: Alzheimer's disease; G protein; PC12 cells; aging; amyloid proteins; apoptosis; biological signal transduction; calcium flux; gene expression; gene mutation; oxidative stress; protein tyrosine kinase; tissue /cell culture

Alzheimer's Disease is a major neurological disorder of the elderly affecting as much as 50% of the population over 80. No cure for this disease is known and its etiology is obscure. A major focus of this project is to discover the role of Amyloid Precursor Protein in neuronal cell death associated with Alzheimer's Disease. Over-expression of mutated forms of this protein (associated with early onset Familial Alzheimer's Disease) in neuronal cells leads to apoptosis. Anti-oxidants prevent this death and an increase in the accumulation of reactive oxygen species in these cells suggests increased oxidative stress as a mechanism of this cell death. Endothelial cells over-expressing mutant proteins show reduced adhesiveness and reduced formation of capillary networks suggesting a functional deficit in cells lining brain capillaries in Alzheimer's Disease.

阿尔茨海默氏病是老年人的主要神经系统疾病 影响80岁以上人口的50％。无法治愈 疾病是已知的，其病因是晦涩的。重点的重点 项目是发现淀粉样蛋白前体蛋白在神经元中的作用 与阿尔茨海默氏病有关的细胞死亡。过表达 该蛋白的突变形式（与早期发作家族性有关 神经元细胞中的阿尔茨海默氏病导致凋亡。抗氧化剂 防止这种死亡并增加活性氧的积累 这些细胞中的物种表明氧化应激增加是一种机制 这个细胞死亡。内皮细胞过表达突变蛋白 显示粘附性降低和毛细管网络的形成降低 提示在细胞内部脑毛细血管的功能缺陷 阿尔茨海默氏病。