ZINC AND ALZHEIMERS AMYLOID CHEMISTRY

锌和阿尔茨海默症淀粉样蛋白化学

• 批准号: 2590801
• 负责人: XUDONG HUANG
• 金额: $ 2.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-11-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2590801
• 关键词: Alzheimer's disease; Animalia; amyloid proteins; emission spectrometry; enzyme linked immunosorbent assay; intermolecular interaction; protein biosynthesis; protein structure function; stoichiometry; tissue /cell culture; western blottings; zinc

The formation of Abeta amyloid in the human brain is considered to be the pathological hallmark of Alzheimer's Disease (AD). Recently, zinc has been discovered to induce Alzheimer's Abeta aggregation both in vitro and in the human cerebrospinal fluid (CSF) at physiological concentrations. However, the chemistry of zinc-initiated Abeta amyloid formation, as well as the neurophysiology of zinc-Abeta interaction, remains to be elucidated. The ultimate goal of this research proposal is to elucidate the chemical mechanism of zinc interaction in the context of the Abeta deposition in AD. The specific aims of this proposal are: to characterize zinc-induced Abeta polymerization and its stoichiometry; to verify the association of abnormal zinc physiology and AD-related biochemical lesions; to identify neurochemical factors that can inhibit zinc-induced Abeta aggregation. To achieve these aims, the chemistry of zinc-Abeta interaction will be studied in vitro, and in cellular and animal systems. Also, potential mechanisms by which zinc (and copper) homeostasis may be disrupted in AD will be studied in human peripheral tissue and in cell cultures. Zinc (and copper) will be measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Abeta will be determined by ELISA and Western blotting. The chemistry and pathophysiology of zinc modulated amyloid formation will be further elucidated under this proposed study.

人类大脑中Abeta淀粉样蛋白的形成被认为是 阿尔茨海默病（AD）的病理标志。最近，锌 已经发现， 体外和生理条件下的人脑脊液（CSF）中 浓度的然而，锌引发的Abeta的化学性质 淀粉样蛋白的形成，以及锌-A β的神经生理学 相互作用，有待进一步研究。这个项目的最终目标 研究建议是阐明锌的化学机制 在AD中A β沉积的背景下的相互作用。的 该提案的具体目标是：表征锌诱导的 Abeta聚合及其化学计量;验证关联 异常锌生理和AD相关的生化病变; 鉴定可抑制锌诱导的Abeta的神经化学因子 聚合来为了实现这些目标，锌-Abeta的化学性质 将在体外、细胞和动物中研究相互作用 系统.此外，锌（和铜） 将在人类中研究AD中体内平衡可能被破坏 外周组织和细胞培养物中。锌（和铜）将是 通过电感耦合等离子体原子发射光谱法测量 （ICP-AES）。将通过ELISA和Western印迹法测定Abeta。 锌调节淀粉样蛋白形成的化学和病理生理学 将在这项拟议的研究中进一步阐明。