Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide β-amyloid (1-42).
Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide β-amyloid (1-42).
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DOI：
10.1098/rsif.2014.0165
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发表时间：
2014-06-06
期刊：
影响因子：
--
通讯作者：
Telling ND
中科院分区：
文献类型：
--
作者：
Everett J;Céspedes E;Shelford LR;Exley C;Collingwood JF;Dobson J;van der Laan G;Jenkins CA;Arenholz E;Telling ND
几十年来，人们已经认识到铁水平升高与阿尔茨海默病（AD）病理学领域之间的联系，包括由肽β-淀粉样蛋白（Aβ）组成的AD病变。尽管有许多关于这种关联的观察，但Aβ和铁之间的关系仍知之甚少。使用X射线显微光谱学，X射线吸收光谱学，电子显微镜和分光光度法铁（II）定量技术，我们研究了Aβ（1-42）和合成铁（III）之间的相互作用，让人想起大脑中的三价铁储存。我们报告Aβ能够在淀粉样蛋白聚集体中积累铁（III），该过程导致Aβ介导的铁（III）还原为氧化还原活性铁（II）相。此外，我们表明，铝的存在增加了Aβ的还原能力，使铁的氧化还原循环。这些结果证明了Aβ蓄积铁的能力，为先前观察到的与AD病变相关的铁浓度局部增加提供了解释。此外，铁从三价铁前体形成氧化还原活性铁相的能力提供了先前在AD组织中观察到的氧化还原活性铁和AD特征性氧化应激水平增加的来源。Aβ和铁之间的这些相互作用为AD进展过程提供了有价值的见解，这最终可能为疾病治疗提供靶点。
For decades, a link between increased levels of iron and areas of Alzheimer's disease (AD) pathology has been recognized, including AD lesions comprised of the peptide β-amyloid (Aβ). Despite many observations of this association, the relationship between Aβ and iron is poorly understood. Using X-ray microspectroscopy, X-ray absorption spectroscopy, electron microscopy and spectrophotometric iron(II) quantification techniques, we examine the interaction between Aβ(1–42) and synthetic iron(III), reminiscent of ferric iron stores in the brain. We report Aβ to be capable of accumulating iron(III) within amyloid aggregates, with this process resulting in Aβ-mediated reduction of iron(III) to a redox-active iron(II) phase. Additionally, we show that the presence of aluminium increases the reductive capacity of Aβ, enabling the redox cycling of the iron. These results demonstrate the ability of Aβ to accumulate iron, offering an explanation for previously observed local increases in iron concentration associated with AD lesions. Furthermore, the ability of iron to form redox-active iron phases from ferric precursors provides an origin both for the redox-active iron previously witnessed in AD tissue, and the increased levels of oxidative stress characteristic of AD. These interactions between Aβ and iron deliver valuable insights into the process of AD progression, which may ultimately provide targets for disease therapies.
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影响因子：
2.7
作者：
Kell DB
通讯作者：
Kell DB
DOI：
10.1196/annals.1306.012
发表时间：
2004-01-01
期刊：
REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS
影响因子：
--
作者：
Huang, XD;Moir, RD;Rogers, JT
通讯作者：
Rogers, JT
影响因子：
3
作者：
Chasteen, ND;Harrison, PM
通讯作者：
Harrison, PM
影响因子：
4
作者：
Gallagher, Joseph J.;Finnegan, Mary E.;Lynch, Marina A.
通讯作者：
Lynch, Marina A.
影响因子：
5.7
作者：
Goedert, M;Sisodia, S S;Price, D L
通讯作者：
Price, D L