ALUMINUM INDUCED INTERACTIONS AND NEUROLOGICAL DISEASE

描述：(申请者摘要)铝一直被怀疑 为了在几种与衰老相关的神经疾病中发挥作用， 但这种联系从来没有明确地建立起来。的确有 有证据表明，铁增强自由基的潜力 铝促进了神经组织中的生成，尽管这 后一种金属没有内在的促氧化剂特性。的意图 这一应用是为了阐明潜在的分子机制。 通过它可以发生这样的增强。络合作用或 任何一种金属相互作用时的蛋白质隔离都将是 检查过了。对这种氧化应激作出反应的生物底物 所诱导的组合金属，将被寻求。这个世界的本质 诱导的活性氧物种将使用酶和 电子自旋共振技术。随后，生物界 铝-铁相互作用的相关性将在动物身上进行调查 单独接触或混合接触这些金属。浓缩物 这些金属在大脑不同区域中的含量将由原子定量 吸收。 试图将铝水平和氧化参数关联起来 老年人和阿尔茨海默病患者的死后脑组织 也会被制造出来。除了研究与氧化有关的参数 对蛋白质的损害，以及给药动物的细胞膜稳定性，以及 经处理的胆碱能神经母细胞瘤细胞，泛素等关键蛋白， β-淀粉样蛋白和热休克蛋白HSP70将通过 免疫学程序。计划中的研究的最后阶段是 一种试图缓解体外和体外诱导的神经组织变化的方法 在体内由这些结合的金属。这将涉及饮食 补充抗氧化剂维生素或使用选择性 螯合剂。结果将阐明铝可能在 与年龄相关的神经疾病的增强。

DESCRIPTION: (Applicant's Abstract) Aluminum has been long suspected to play a role in several neurological diseases associated with aging, but this linkage has never been unequivocally established. There is evidence that the potential of iron for enhancing free radical generation in nervous tissue is enhanced by aluminum, although this latter metal has no intrinsic pro-oxidant properties. The intent of this application is to illuminate the underlying molecular mechanisms by which such a potentiation may take place. The effect of chelation or protein sequestration of either metal upon their interactions will be examined. The biological substrate responsive to such oxidative stress induced by the combined metals, will be sought. The nature of the induced reactive oxygen species will be documented using both enzymic and electron spin resonance techniques. Subsequently, the biological relevance of aluminum-iron interactions will be investigated in animals exposed to these metals singly or in combination. The concentrations of these metals in various brain regions will be quantitated by atomic absorption. An attempt to correlate levels of aluminum and oxidative parameters in human post-mortem cerebral tissue from aged and Alzheimer's brains will also be made. In addition to study of parameters relating to oxidative damage to proteins, and membrane stability in dosed animals, and in treated cholinergic neuroblastoma cells, key proteins such as ubiquitin, beta-amyloid, and heat shock protein HSP 70, will be quantitated by immunological procedures. The final phase of the planned research is an attempted mitigation of changes induced in neural tissue in vitro and in vivo by these combined metals. This will involve dietary supplementation with antioxidant vitamins or the use of selective chelators. Results will illuminate the role that aluminum may play in potentiation of age-related neurological diseases.