ROLE OF ABETA-PROTEIN AND METAL INTERACTIONS IN ALZHEIMER?S DISEASE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 该项目正在研究阿尔茨海默病多肽A-β与其他蛋白之间的蛋白质-蛋白质相互作用，如α-B晶体蛋白，它可能介导阿尔茨海默病的神经毒性，以及与金属的相互作用。蛋白质印迹提供了A-β和α-B-晶体蛋白在AD沉积中共定位的一些证据。初步证据表明，α-B晶体蛋白阻止了A-β纤维的形成，并增强了重组人A-β1-42的神经毒性。目前正在进行利用纯化的蛋白质和质谱学方法在体外鉴定单抗-AB晶体蛋白交联物(S)的实验。如果这被证明是成功的，以后的实验将探索人类组织样本中是否存在这种交联物。最近的实验已经开始使用2D-MALDI-TOF MS/MS来探索蛋白质在小鼠脑中的空间分布，这已经通过电感耦合等离子体质谱来定位金属的分布。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is investigating the protein-protein interactions between the Alzheimer's peptide A-beta and other prtoeins, such as alpha-B crystallin, which may mediate neurotoxicity in Alzheimer's disease, and with metals. Western blots have provided some evidence for colocalization of A-beta and alpha-B-crystallin in AD deposits. Preliminary evidence indicates that alpha-B crystallin blocks A-beta fibril formation and potentiates the neurotoxicity of recombinant human A-beta 1-42. Experiments are now underway to identify Ab-aB crystallin crosslink signature(s) in vitro using purified proteins and mass spectrometry. If this proves successful, later experiments will explore the occurrence of such crosslinks in human tissue samples. Recent experiments have begun to use 2D-MALDI-TOF MS/MS to explore the spatial distribution of proteins in mouse brain which has already been analyzed by ICP-MS to locate metal distributions.