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: 6509922
• 负责人: GRACE Y SUN
• 金额: $ 86.87万
• 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 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6509922
• 关键词: 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：阿尔茨海默病？S病(AD)是最昂贵和最具破坏性的疾病 21世纪的神经退行性疾病。要战胜阿尔茨海默病，治疗必须 可用于预防该病的神经病理表现。 人们普遍认为阿尔茨海默病(AD)脑内β淀粉样蛋白(AB)斑块积聚 导致涉及神经胶质细胞的氧化损伤和炎症反应 激活，进而导致神经细胞死亡。很多因素， 包括载脂蛋白、磷脂和胆固醇，可以影响 AB的聚集及其细胞毒作用。有证据表明他们扮演的角色 细胞质膜脂质和G蛋白偶联受体功能的研究 AB在AD脑内的细胞毒作用。该项目的主要基因座 项目拨款(PPG)是1)检查AB和氧化剂应激源的影响 与AD表型相关的神经细胞功能，包括激活 磷脂酶、环氧合酶和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。 这部高度集成的PPG由Grace Sun博士执导，由 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 磷脂酶A2介导的神经细胞炎症反应。 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细胞和神经元中的作用 细胞。项目3(G.Wood，PL)将确定AB如何影响胆固醇 细胞膜和亚细胞内的动态平衡、运输和分布 细胞器。通过了解脂类、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 提供将影响……发展的重要新信息 治疗这种衰弱疾病的有效药物疗法。