The role of Hsp 90 in Alzheimer's Disease

Hsp 90 在阿尔茨海默病中的作用

基本信息

批准号：
8058757
负责人：
WENJIE LUO
金额：
$ 13.35万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-15 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8058757
关键词：
Affect Affinity Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Amyloid Amyloid beta-Protein Precursor Animal Model Animals Behavior Binding Biochemistry Biological Process Blood - brain barrier anatomy C-terminal Cell Line Cellular biology Chemistry Chronic Clinical Cultured Cells Data Deposition Development Disease Disease Progression Disease model Drug Kinetics Economic Burden Educational workshop Electrophysiology (science)Event Generations Goals HSP 90 inhibition Head Heat-Shock Proteins 90 Impaired cognition Investigation Knowledge Laboratories Learning Mediator of activation protein Memory Loss Mentors Mentorship Metabolism Microglia Modeling Molecular Molecular Chaperones Mus Mutagenesis Mutation Nerve Degeneration Neurodegenerative Disorders Neurons Neurosciences Neurosciences Research Outcome Pathology Pharmacology Phosphorylation Phosphotransferases Prevalence Process Proteins Proteolytic Processing Reading Regulation Research Research Personnel Research Training Role Signaling Molecule Structure Testing Therapeutic Therapeutic Effect Training Universities age related amyloid formation amyloid precursor protein processing base career experience genetic inhibitor in vivo inhibitor/antagonist lectures meetings mouse model mutant neurodegenerative phenotype neurofibrillary tangle formation neuron loss neurotoxic novel therapeutics protein complex protein folding protein metabolism protein misfolding protein transport public health relevance secretase social tau Proteins tau mutation tool trafficking

项目摘要

DESCRIPTION (provided by applicant): The goal of the proposed research is to investigate the role of Hsp90 in regulating amyloid generation associated with AD progression. Utilizing this knowledge, my long-term research goal is to understand the molecular mechanisms of disease progression in AD and search for therapeutic tools. A five-year research and training plan has been developed to meet these goals. This plan consists of training in animal pathology and behavior involved in AD progression. This plan will be implemented under the mentorship of the primary mentor, an expert in neuroscience research and neurodegeneration, and a co-mentor, an expert in Hsp90 biological function and Hsp90 inhibitor chemistry. The training will be supplemented by an expert in AD pathology and an expert in electrophysiology. The training will consist of structured readings, attendance at course lectures and seminars, structured laboratory experience and presentations at academic meetings. With complete support from my lab head and the university vice president, I will have access to a fully equipped laboratory of molecular and cellular neuroscience. The proposed research will test the hypothesis that the dysregulated cellular events occurring in AD development are dependent on Hsp90 for disease progression. Specific aims will: 1) characterize Hsp90-APP interaction and its regulation of A2 formation; 2) investigate Hsp90-regulated APP metabolism; and 3) the therapeutic effects of Hsp90 inhibitor on the pathology and electrophysiology abnormality of AD model mice. PUBLIC HEALTH RELEVANCE: Alzheimer's disease is the most common age-related neurodegenerative disorder. This disease causes memory loss and cognitive impairment. AD is the major clinical, social and economic burden and its prevalence is increasing dramatically. The goal of this research is to provide tools for interfering in this devastating research.

描述（由申请人提供）：拟议研究的目标是研究 Hsp90 在调节与 AD 进展相关的淀粉样蛋白生成中的作用。利用这些知识，我的长期研究目标是了解 AD 疾病进展的分子机制并寻找治疗工具。为了实现这些目标，我们制定了五年研究和培训计划。该计划包括 AD 进展中涉及的动物病理学和行为方面的培训。该计划将在主要导师（神经科学研究和神经退行性疾病专家）和副导师（Hsp90生物功能和Hsp90抑制剂化学专家）的指导下实施。培训将由 AD 病理学专家和电生理学专家进行补充。培训将包括结构化阅读、参加课程讲座和研讨会、结构化实验室体验以及学术会议上的演讲。在实验室负责人和大学副校长的全力支持下，我将能够使用设备齐全的分子和细胞神经科学实验室。拟议的研究将验证 AD 发展过程中发生的失调细胞事件依赖于 Hsp90 来促进疾病进展的假设。具体目标将： 1) 表征 Hsp90-APP 相互作用及其对 A2 形成的调节； 2）研究Hsp90调节的APP代谢； 3)Hsp90抑制剂对AD模型小鼠病理及电生理异常的治疗作用。公共卫生相关性：阿尔茨海默病是最常见的与年龄相关的神经退行性疾病。这种疾病会导致记忆丧失和认知障碍。 AD 是主要的临床、社会和经济负担，其患病率正在急剧增加。这项研究的目标是提供干扰这项毁灭性研究的工具。