Signaling Transduction and Alzheimer's Disease

信号转导与阿尔茨海默病

• 批准号: 7342758
• 负责人: PAUL GREENGARD
• 金额: $ 136.87万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342758
• 关键词: Signaling; Transduction; Alzheimer; Disease

DESCRIPTION (provided by applicant): This is the second competing renewal of our Program Project Grant (PPG), entitled, "Signal Transduction and Alzheimer's Disease". This PPG was developed from a program established in the Laboratory of Molecular and Cellular Neuroscience in 1990 for the purpose of investigating the biochemistry, cell biology, molecular biology, and pharmacology of regulation, by protein phosphorylation, of the Alzheimer amyloid precursor protein (APP). Studies of the cellular and molecular mechanisms underlying the sequential cleavage of the APP to ¿-amyloid (A¿) by ¿-and ?-secretases have afforded great insight into the etiology of Alzheimer's Disease (AD).Understanding the mechanisms that regulate A¿ generation may enable the development of pharmacologically active compounds that target A¿ formation. A group of experts in various disciplines of biomedical research will carry out these studies using distinct but complementary approaches. Project 1, entitled "Effects of A¿ on Synaptic Structure, Transmission and Plasticity", will investigate the effects of A¿ on dendritic spine morphology, glutamate receptor trafficking, and long term potentiation in cellular and mouse models of AD. Project 2, entitled "Mechanisms of ?-Secretase Regulation" will characterize the underlying mechanism(s) by which ATP, and ATP analogs, including Gleevec, regulate ¿APP processing and trafficking. Project 3, entitled "Role of CK1 in Alzheimer Disease Etiology" will evaluate the role of the protein kinase, CK1, in ¿APP processing, and identify the targets for CK1 involved in this process. These studies will be supported by a Scientific Core (Core B) that will produce key materials and perform routine, yet critical, tasks that will be required to accomplish the studies described in the other Projects. An Administrative Core (Core A) will coordinate various aspects of the PPG, integrating day-to-day activities of the investigators and consultants involved in the various projects. These studies will lead to greater knowledge of mechanisms involved in the production of A¿ in the brains of AD patients and will hopefully identify novel proteins that can be targeted by therapeutic agents. REVIEW OF INDIVDUAL COMPONENTS CORE A - ADMINISTRATIVE CORE; Dr. Paul Greengard (CL) DESCRIPTION (provided by applicant): The objective of the NIA Program Project funding mechanism is to provide for greater opportunities and capabilities through the unification of a shared commitment to a central investigative theme. The main goal of the Administrative Core is to facilitate and support the unification and interaction of the scientists and administrative personnel working on the Proposal at The Rockefeller University, Weill College of Cornell University and Yale University School of Medicine. Specific Aims: Aim I. Coordination of and communication among between the Cores and Projects in the Proposal - Facilitate communication between the three Projects and two Cores, the scientific and administrative staffs at Rockefeller, Cornell and Yale and consultants from other institutions - Schedule and coordinate all formal meetings - Facilitate the transfer of information for data sharing and manuscript generation - Career development coordination center for students and postdoctoral trainees Aim II. Maintenance of the Physical Working Space, Supplies and Equipment for the Proposal - Maintenance of the physical laboratory and administrative space - Oversight of the laboratory safety guidelines - Purchase and maintenance of supply stocks Aim III. Data and Progress Record Maintenance and Clerical Support for the Proposal - Clerical support and record maintenance - Maintenance of project-generated resources files - Publication generation and archive - Supply and equipment record maintenance - Budget tracking and allocation for the Cores and Projects - Data sharing of biological material resources and tools generated by the NIA Program Project Grant

描述（应用程序提供）：这是我们计划项目赠款（PPG）的第二次竞争续约，标题为“信号转导和阿尔茨海默氏病”。该PPG是由1990年在分子和细胞神经科学实验室中建立的一个程序开发的，目的是研究通过蛋白质磷酸化的生物化学，细胞生物学，分子生物学和调节的药物，该蛋白质磷酸化，阿尔茨海默氏菌淀粉样蛋白前体蛋白（App）。对应用程序的顺序裂解的细胞和分子机制的研究，通过€ - - ？ - 分泌酶对阿尔茨海默氏病的病因（AD）的病因有很大的了解，可以实现A emands a的机制。一群生物医学研究学科的专家将使用不同但完整的方法进行这些研究。项目1的标题为“ A对突触结构，传播和可塑性的影响”将研究A检测A对树突状脊柱形态，谷氨酸受体运输的影响，以及在AD的细胞和小鼠模型中的长期潜在。项目2，标题为“ - 分泌酶调节的机制”，将表征基本机制，其中ATP和ATP类似物（包括Gleevec）调节了应用程序处理和运输。项目3，题为“ CK1在阿尔茨海默氏病病因中的作用”将评估蛋白激酶，CK1在“应用程序处理中”的作用，并确定参与此过程中涉及的CK1的靶标。这些研究将得到科学核心（核心B）的支持，该科学核心将产生关键材料并执行常规但至关重要的任务，以完成其他项目中描述的研究所需的任务。行政核心（核心A）将协调PPG的各个方面，并整合参与各个项目的调查人员和顾问的日常活动。这些研究将导致对AD患者大脑中A涉及的机制的更多了解，并希望鉴定出可以由治疗剂靶向的新型蛋白质。 审查不合格组件 核心A-管理核心；保罗·格林加德博士（CL） 描述（由应用程序提供）：NIA计划项目资金机制的目的是通过统一对中央调查主题的共同承诺来提供更大的机会和能力。行政核心的主要目标是支持和支持洛克菲勒大学，康奈尔大学威尔大学和耶鲁大学医学院的科学家和行政人员的统一和互动。 具体目的： AIM I.提案中核心与项目之间的协调和沟通 - 促进三个项目和两个核心之间的沟通，洛克菲勒，康奈尔和耶鲁大学的科学和行政人员以及其他机构的顾问 - 安排并协调所有正式会议 - 促进信息共享和手稿生成的信息传输 - 针对学生和博士后学员的职业发展协调中心 目标II。维护实体工作空间，供应和设备 - 维护实验室和行政空间 - 监督实验室安全指南 - 购买和维护供应库存 目标三。数据和进度记录维护和对该提案的文书支持 - 文书支持和记录维护 - 维护项目生成的资源文件 - 出版和档案 - 供应和设备记录维护 - 核心和项目的预算跟踪和分配 - NIA计划项目赠款生成的生物材料资源和工具的数据共享