Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?
Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?
复制标题
DOI：
10.1016/s0891-5849(99)00016-7
复制
发表时间：
1999-06-01
影响因子：
7.4
通讯作者：
Perry, G
中科院分区：
文献类型：
--
作者：
Castellani, RJ;Smith, MA;Perry, G
阿尔茨海默病（AD）最显著的特征之一是铁在神经元缠结和老年斑中的积累。有趣的是，这种铁被发现为铁（II）和铁（III），并且具有氧化还原活性。为了解决这种铁是否参与氧化还原循环的问题，必须研究铁（II）如何积累，因为铁（II）的氧化会导致活性氧的产生。为了开始解决这个问题，在这里，我们研究了血浆铜蓝蛋白，一种通过将铁（II）转化为铁（III）来调节铁的氧化还原状态的关键蛋白质。AD病例和年龄匹配的对照组，在尸检中获得相似的死后间隔，显示出相似的铜蓝蛋白免疫反应性水平，主要局限于神经元。然而，在显着的对比，AD的情况下，显示显着增加血浆铜蓝蛋白内的neuroplastin通过免疫印迹分析的组织匀浆，以及普遍增加neuroplastin染色确定。总之，这些研究结果表明，神经元诱导的血浆铜蓝蛋白是微弱的AD，即使有组织的血浆铜蓝蛋白的增加。因此，神经元铜蓝蛋白对铁的反应失败可能是导致AD神经元中氧化还原活性铁积累的重要因素。(C)1999 Elsevier Science Inc.
One of the most striking features of Alzheimer disease (AD) is an accumulation of iron in neurofibrillary tangles and senile plaques. Intriguingly, this iron is found as both iron (II) and iron (III) and is redox-active. To address the issue of whether such iron participates in redox cycling, it was essential to investigate how iron (II) accumulates, since oxidation of iron (II) can lead to the generation of reactive oxygen species. To begin to address this issue, here we investigated ceruloplasmin, a key protein involved in the regulation of the redox state of iron by converting iron (II) to iron (III). Cases of AD and age-matched controls, obtained at autopsy with similar postmortem intervals, display similar levels of ceruloplasmin immunoreactivity that is mainly confined to neurons. However, in marked contrast, cases of AD show a significant increase in ceruloplasmin within the neuropil determined by immunoblot analysis of tissue homogenates as well as a generalized increased neuropil staining. Together, these findings suggest that neuronal induction of ceruloplasmin is feeble in AD, even while there is an increase in tissue ceruloplasmin. Therefore, a failure of neuronal ceruloplasmin to respond to iron may be an important factor that then leads to an accumulation of redox-active iron in neurons in AD. (C) 1999 Elsevier Science Inc.