HYDROGEN EXCHANGE STUDIES ON A BETA AMYLOID FIBRILS

该研究计划代表了理解蛋白质聚集相关疾病（包括阿尔茨海默病、亨廷顿病和帕金森病）的整体努力的重要组成部分。在患有这些疾病的患者中发现了蛋白质聚集和正常可溶性蛋白质的异常组织沉积。重要的是要了解这些聚集体的结构和功能，以便设计诊断和治疗这些疾病的方法。这一建议涉及研究淀粉样原纤维的结构，淀粉样原纤维是一种与阿尔茨海默病有关的聚集体。包括氢氘交换质谱和微尺度分离技术在内的分析技术将用于确定阿尔茨海默病中存在的淀粉样原纤维中的氢键和β -片网络的程度。

DESCRIPTION This research proposal represents an important part of the overall effort to understand protein aggregation associated diseases, including Alzheimer's, Huntington's and Parkinson's Diseases. Protein aggregates and abnormal tissue deposits of normally soluble proteins have been found in the patients suffering from these disease. It is important to understand the structure and function of these aggregates in order to devise methods for diagnosis and cures for these diseases. This proposal addresses studying the structure of amyloid fibrils, a type of aggregate, which is associated with Alzheimer's Disease. Analytical techniques including hydrogen deuterium exchange mass spectrometry and microscale separation techniques will be utilized to define the hydrogen bonding and extent of beta-sheet network in the amyloid fibrils present in Alzheimer's Disease.