Cell models for AD:Lipids and related signaling pathways

AD 细胞模型：脂质和相关信号通路

• 批准号: 6882626
• 负责人: GRACE Y SUN
• 金额: $ 95.21万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882626
• 关键词: Alzheimer' s disease; amyloid proteins; Alzheimer' s disease; amyloid proteins

DESCRIPTION: Alzheimer?s disease (AD) is the most costly and devastating neurodegenerative disorder of the 21st century. To conquer AD, therapies must be developed to prevent the neuropathological manifestations of the disease. It is widely held that accumulation of beta amyloid (AB) plaques in AD brain causes oxidative damage and inflammatory responses involving glial cell activation that, in turn, leads to neuronal cell death. Many factors, including apolipoproteins, phospholipids and cholesterol, can influence aggregation of AB and its cytotoxic actions. There is evidence for the roles of plasma membrane lipids and G protein-coupled receptor functions in the cytotoxic effects of AB in the AD brain. The major loci of this Program Project Grant (PPG) are 1) to examine the effects of AB and oxidant stressors on neural cell functions relevant to the AD phenotype, including activation of phospholipases, cyclo-oxygenases and G protein-coupled receptors, and 2) to determine relationships between cholesterol homeostasis, lipoproteins and AD. This highly integrated PPG, directed by Dr. Grace Sun, consists of an Administrative Core, a Cell Culture Core and three research projects. Project #1 (G. Sun, PL) will determine the effects of AB and lipoproteins on oxidative and inflammatory responses in neural cells mediated by phospholipases A2. Project #2 (G. Weisman, PL) will determine the effects of AB and lipoproteins on G protein-coupled P2Y2 nucleotide receptor functions in glial and neuronal cells. Project #3 (G. Wood, PL) will determine how AB affects cholesterol homeostasis, transport and distribution in cell membranes and subcellular organelles. By understanding the role of lipids, lipoproteins, and receptor-mediated cell signaling pathways in AD pathology, the proposed studies will provide important new information that will impact the development of effective pharmacotherapies for this debilitating disease.

描述：阿尔茨海默氏病（AD）是最昂贵和毁灭性的 21世纪的神经退行性障碍。要征服广告，疗法必须 开发以防止该疾病的神经病理表现。 人们普遍认为，AD大脑中β-淀粉样蛋白（AB）斑块的积累 引起氧化损伤和涉及神经胶质细胞的炎症反应 激活反过来导致神经元细胞死亡。许多因素， 包括载脂蛋白，磷脂和胆固醇可能会影响 AB及其细胞毒性作用的聚集。有证据表明角色 质膜脂质和G蛋白偶联受体功能 AB在AD大脑中的细胞毒性作用。该计划的主要基因座 项目赠款（PPG）为1）检查AB和氧化应激源的影响 关于与AD表型相关的神经细胞功能，包括激活 磷脂酶，环氧酶和G蛋白偶联受体，以及2） 确定胆固醇稳态，脂蛋白和AD之间的关系。 由格蕾丝·孙（Grace Sun）执导的高度整合的PPG由一个 行政核心，一个细胞培养核心和三个研究项目。项目 ＃1（G. Sun，PL）将确定AB和脂蛋白对氧化的影响 以及由磷脂酶A2介导的神经细胞中的炎症反应。 项目＃2（G. Weisman，PL）将确定AB和脂蛋白的影响 G蛋白偶联的P2Y2核苷酸受体在神经胶质和神经元中的功能 细胞。项目＃3（G. Wood，PL）将确定AB如何影响胆固醇 稳态，细胞膜和亚细胞的运输和分布 细胞器。通过了解脂质，脂蛋白和受体介导的作用 AD病理中的细胞信号通路，拟议的研究将 提供重要的新信息，以影响 这种令人衰弱的疾病的有效药物疗法。