BIOLOGICAL MECHANISMS OF ALUMINUM NEUROTOXICITY

地表沃茨因酸雨而酸化， 从矿物质中释放出大量的铝离子 沿着人们对高血压的关注 酸化沃茨中的铝离子浓度 明确证明了铝与 铝离子在人体内的几种病理状态。 与多种神经、骨骼和心血管疾病有关 具有明显环境病因的疾病。 这项建议 将侧重于生物化学过程的阐明， 铝离子表达的分子机制 其强大且通常具有选择性的神经毒性。 我们建议 在临界温度下，铝离子将取代镁离子 和调节位点， 用于镁离子依赖过程。 重要的是， 游离铝离子浓度，而非总铝离子负荷 或铝离子种类，这对表达 病理过程。 因此，选择性神经毒性可以 是增强的铝离子浓度的结果（不是 累积）在神经组织中相对于血清或增强的 神经组织中镁离子依赖过程的敏感性 铝离子介导的抑制。 我们的努力将解决 这两个问题的重点是审查代理人， 神经组织中的蛋白质，相对于血清，可能有助于 提高铝离子浓度， “缓冲”和铝对镁离子的抑制作用- 神经组织中与磷酸盐有关的依赖酶 转移

The acidification of surface waters through acid precipitation has served to dramatically release aluminum ion from mineral stores. Along with the increasing concern over appearance of high aluminum ion concentrations in acidified waters has been the unequivocal demonstration of an association of aluminum with severla pathological states in man. Aluminum ion has been implicated in a variety of neurological, skeletal and cardiovascular disorders with an apparent environmental etiology. This proposal will focus on elucidation of the biochenical processes and molecular mechanisms through which alumunimun ion may express its potent and often selective neurotoxicity. We propose that aluminum will substitute for magnesium ion at critical enzume and regulatory sites with a concommitant depression of the rates for the magnesium ion-dependent processes. Importantly, it is the concentrationof free aluminum ion, not total aluminum ion burden or aluminum ion species, that is critical to expression of the pathological process. The selective neurotoxicity could therefore be a consequence of enhanced alunimun ion concentration (not accumulation) in neural tissue relative to serum or of an enhanced sensitivity of magnesium ion-dependent processes in neural tissue to aluminum ion-mediated inhibition. Our efforts will address both of these issues and focus on examination of agents and proteins in neural tissue, relative to serum, that may serve to enhance aluminum ion concentrations and minimize aluminum ion "buffering" and on the inhibition by aluminum of magnesium ion- dependent enzymes in neural tissue involved in phosphate transfer.