ALUMINUM INDUCED INTERACTIONS AND NEUROLOGICAL DISEASE

点击翻译按钮获取中文摘要

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.