ZINC AND ALZHEIMERS AMYLOID CHEMISTRY

人脑中Aβ淀粉样蛋白的形成被认为是 阿尔茨海默病(AD)的病理特征。最近，锌 已经被发现可以诱导阿尔茨海默氏症的Abeta聚集 体外和生理状态下的人脑脊液(CSF)中 浓度。然而，锌引发的Abeta的化学 淀粉样蛋白的形成以及锌-Aβ的神经生理学 相互作用，还有待阐明。这样做的最终目的是 研究建议是阐明锌的化学机理 AD中Abeta沉积背景下的相互作用。这个 这项提议的具体目标是：表征锌诱导的 Aβ聚合及其化学计量；以验证关联 锌的生理异常和AD相关的生化损害； 确定可抑制锌诱导的Abeta的神经化学因素 聚合。为了实现这些目标，锌-Abeta的化学 相互作用将在体外、细胞和动物中进行研究。 系统。此外，锌(和铜)的潜在机制 阿尔茨海默病的体内平衡可能被破坏将在人类身上进行研究 外周组织和细胞培养中。锌(和铜)将是 电感耦合等离子体原子发射光谱分析 (电感耦合等离子体原子发射光谱仪)。用酶联免疫吸附试验和免疫印迹法检测Aβ。 锌调控淀粉样蛋白形成的化学和病理生理 将在这项拟议的研究中进一步阐明。

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.