ALUMINUM ION BINDING--ALZHEIMER'S AND RELATED DISORDERS

这项研究项目涉及到对化学和 铝离子的生物化学及其可能性的评估 参与神经功能障碍，如阿尔茨海默病和 透析性脑病。铝离子可能作为一种 防龋剂在预防牙菌斑形成方面也会 地址。另一个长期目标是评估 铝过量可能对钙代谢产生干扰。这个 该项目的具体目标是：研究铝的络合作用 通过核苷酸来提供了解结合的基础 脑神经细胞中核酸对铝的抑制作用 铝-三磷酸腺苷的磷酸转运酶及其抑制作用 铝离子，参与调节蛋白质水平的酶 神经递质，以获得可能的抑制部位的信息 指铝的代谢；研究铝离子的络合作用 几组简单的、多齿的螯合剂，以帮助设计 可用于抗铝药物的特定铝络合剂 心理治疗。该项目的具体目标将通过具有约束力的 研究将提供有关数量的信息 酶、核苷酸和铝离子结合部位的亲和力 多齿螯合剂。将进行动力学研究，以 评估铝络合物对酶活性的影响 在磷酰化转移反应中的作用和对 某些神经递质的水平。磁共振研究将是 这将产生有关解决方案结构的信息 这些铝络合物。这些技术结合在一起将提供 这些信息将极大地提高我们对 铝离子的化学和生物化学，并应提供依据 关于铝和其他金属离子影响的更详细的研究 在新陈代谢方面。

This research project involves an examination of the chemistry and biochemistry of aluminum ions and an assessment of their possible involvement in neurological dysfunctions such as Alzheimer's disease and dialysis encephalopathy. The possible involvement of aluminum ions as a cariostatic agent in the prevention of dental plaque formation will also be addressed. An additional long term objective is an evaluation of the possible interference of calcium metabolism by excess aluminum. The specific aims of this project are to: examine the complexation of aluminum by nucleotides to provide the basis for understanding the binding of aluminum by nucleic acids in brain nerve cells; survey the inhibition of phosphoryl-transferring enzymes by aluminum-ATP and the inhibition, by aluminum ions, of enzymes involved in regulating the levels of neurotransmitters to obtain information on the possible sites of inhibition of metabolism by aluminum; study the complexation of aluminum ions by several groups of simple, multidentate chelators to aid in the design of specific aluminum chelators that can function in anti-aluminum drug therapy. The specific aims of this project will be addressed by binding studies that will provide quantitative information about the number of affinity of binding sites for aluminum ions to enzymes, nucleotides, and multidentate chelators. Kinetic studies will be conducted that will evaluate the effect of aluminum complexes on the activity of enzymes that function in phosphoryl-transfer reactions and in the regulation of the levels of certain neurotransmitters. Magnetic resonance studies will be carried out that will yield information about the solution structures of these aluminum complexes. Together these techniques will provide information that will dramatically improve our understanding of the chemistry and biochemistry of aluminum ions, and should provide the basis for more detailed studies into the effects of aluminum and other metal ions on metabolism.