ROLE OF ABETA-ALPHAB CRYSTALLIN INTERACTIONS IN ALZHEIMER?S DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目正在研究阿尔茨海默氏症多肽A-β和α-B晶体蛋白之间的蛋白质-蛋白质相互作用，这可能介导阿尔茨海默病的神经毒性。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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is investigating the protein-protein interactions between the Alzheimer's peptide A-beta and alpha-B crystallin, which may mediate neurotoxicity in Alzheimer's disease. 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.