Mechanisms of Abeta Sequestration in AD

描述（由申请人提供）：PA-00-019指导研究科学家发展奖（K 01）“AD中Abeta螯合的机制” 候选人Yasuji Matsuoka博士是一名初级研究员，在阿尔茨海默病（AD）的神经科学研究方面具有相当丰富的经验。为了成为AD和其他神经退行性疾病的完全独立的翻译神经科学家，额外的监督培训期至关重要。候选人渴望扩展他在临床和治疗研究基础方面的知识和技术。Paul Aisen博士（神经病学和医学教授，乔治敦大学记忆障碍项目主任）将成为AD药物开发培训的主要导师。Karen Gale博士（乔治敦大学药理学教授）和Karen Duff博士（Nathan Kline研究所/纽约大学副教授）将担任共同导师，提供使用阿尔茨海默病转基因模型进行行为分析的培训。其他顾问将提供神经变性（Mattson博士），药物化学（Kozikowski博士）和神经影像学（Dr. Reyke）基础研究的专业知识乔治敦大学医学中心提供了一个刺激的科学和临床环境。五年的职业发展计划旨在：1）为候选人提供临床药物开发方面的深刻理解和背景; 2）提高和扩展他在AD小鼠模型行为分析方面的研究经验和知识; 3）确保使用人类受试者和动物进行临床和基础研究的道德行为。 该提案的主要研究目标是阐明一种有前途的新型AD治疗方法“Abeta螯合”。这位候选人已经证明，大脑Aa可以使用非免疫淀粉样蛋白结合化合物来改变。拟议的研究将调查Aa的库和构象，这些库和构象可能受到外周结合化合物的影响，这些化合物的理想结构，以及Abeta的血脑屏障转运。

DESCRIPTION (provided by applicant): PA-00-019 Mentored Research Scientist Development Award (K01) "Mechanisms of the Abeta sequestration in AD" The candidate, Yasuji Matsuoka, PhD, is a junior researcher with considerable experience in neuroscience research in Alzheimer's disease (AD). In order to become a fully independent translational neuroscientist in AD and other neurodegenerative diseases, an additional supervised training period is critical. The candidate is eager to expand his knowledge and techniques in both clinical and basic aspects of therapeutic research. Dr. Paul Aisen (Professor of Neurology and Medicine, and Director of the Memory Disorders Program at Georgetown University), will be the primary mentor for training in drug development for AD. Drs. Karen Gale (Professor of Pharmacology, Georgetown University) and Karen Duff (Associate Professor, Nathan Kline Institute / New York University) will be co-mentors to provide training in behavioral analysis using transgenic models of Alzheimer's disease. Additional consultants will provide expertise in basic research into neurodegeneration (Dr. Mattson), medicinal chemistry (Dr. Kozikowski) and neuroimaging (Dr. Fricke) Georgetown University Medical Center offers a stimulating scientific and clinical environment. The five year career development plan aims to: 1) provide the candidate a strong understanding and background in clinical drug development; 2) improve and extend his research experience and knowledge in behavioral analysis of AD mouse models; 3) assure ethical conduct in both clinical and basic research using human subjects and animals. The primary research goal of this proposal is the elucidation of a promising, novel therapeutic approach to AD, "Abeta sequestration". The candidate has demonstrated that brain Aa can be altered using non-immune amyloid-binding compounds. The research studies proposed will investigate the pools and conformations of Aa that can be influenced by peripheral binding compounds, the ideal structure of such compounds, and blood-brain barrier transport of Abeta.