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

ABETA-ALPHAB 晶状体蛋白相互作用在阿尔茨海默病中的作用

• 批准号: 7955969
• 负责人: LEE E. GOLDSTEIN
• 金额: $ 0.95万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955969
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Biology; Computer Retrieval of Information on Scientific Projects Database; Crystallins; Deposition; Funding; Grant; Human; In Vitro; Institution; Mass Spectrum Analysis; Mediating; Medicine; Proteins; Recombinants; Research; Research Personnel; Resources; Role; Source; Tissue Sample; United States National Institutes of Health; Western Blotting; alpha-Crystallin B Chain; crosslink; human tissue; neurotoxicity; peptide A; protein protein interaction; research study

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目正在研究阿尔茨海默病肽 A-β 和 α-B 晶状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。蛋白质印迹为 AD 沉积物中 A-β 和 α-B-晶状体蛋白的共定位提供了一些证据。初步证据表明，α-B 晶状体蛋白可阻断 A-β 原纤维形成并增强重组人 A-β 1-42 的神经毒性。目前正在进行实验，利用纯化蛋白和质谱在体外鉴定 Ab-aB 晶状体蛋白交联特征。如果证明成功，后续实验将探索人体组织样本中这种交联的发生。