RUI: Aging & Biochemistry of a New Receptor Protein in Brain

芮：老龄化

• 批准号: 8719741
• 负责人: Lawrence Duffy
• 金额: $ 10.73万
• 依托单位: University of Alaska Fairbanks Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-15 至 1991-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8719741&HistoricalAwards=false
• 关键词: RUI; Aging; & Biochemistry; New

This study is the initial phase in a project which seeks to understand the molecular aging of brian receptor proteins. Dr. Duffy has chosen a receptor protein recently reported to be the precursor to the amyloid deposits found in aging mammalian brains. Preliminary studies by others indicate that the gene is highly conserved across species and appears to be expressed in many different cell types, including neurons. In this initial phase, Dr. Duffy will survey a variety of cell types, including endothelial cells, glial, neurons and fibroblasts to see if the protein is expressed in sufficient quantities for biochemical studies. Quantitation will be performed by isolating the protein using modern FPLC procedures devised for membrane proteins. Purification of this receptor protein will be followed using antibodies raised to various regions of the human protein, based on the DNA-derived sequence. Dr. Duffy will supplement these antibodies by the production of monoclonal antibodies to the purified receptor. While these studies to find a suitable model system are in progress, Dr. Duffy will study the necessary elements of amyloid formation using a series of peptide analogues to the 40 amino acid amyloid fragment. The effect of different amino acids on the structure of amyloid will be monitored using EM, x-ray and NMR methodologies.

这项研究是一个项目的初始阶段，该项目旨在 了解大脑受体蛋白的分子老化。 博士 达菲选择了一种受体蛋白，最近有报道称， 在衰老的哺乳动物中发现的淀粉样蛋白沉积物的前体 大脑 其他人的初步研究表明， 在物种间高度保守，似乎在 包括神经元在内的多种细胞类型。 在该初始 达菲博士将调查各种细胞类型，包括 内皮细胞，神经胶质细胞，神经元和成纤维细胞，看看是否 蛋白质以足够的量表达， 问题研究 通过分离蛋白质进行定量 使用为膜蛋白设计的现代FPLC程序。 该受体蛋白的纯化将随后使用 针对人类蛋白质不同区域的抗体， DNA衍生序列上 达菲医生会补充这些 通过生产针对该抗体的单克隆抗体， 纯化受体 虽然这些研究找到了一个合适的模式， 系统正在进行中，达菲博士将研究必要的 使用一系列肽类似物的淀粉样蛋白形成的要素 40个氨基酸的淀粉样蛋白片段 了不同 氨基酸对淀粉样蛋白结构的影响将通过使用 EM、X射线和NMR方法。