A prochelator activated by hydrogen peroxide prevents metal-induced amyloid Beta aggregation.
A prochelator activated by hydrogen peroxide prevents metal-induced amyloid Beta aggregation.
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DOI：
10.1002/cbic.200900597
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发表时间：
2010-01-04
期刊：
影响因子：
3.2
通讯作者：
Franz, Katherine J.
中科院分区：
文献类型：
--
作者：
Dickens, Marina G.;Franz, Katherine J.
阿尔茨海默氏症是一种进行性和致命的脑部疾病，是痴呆症最常见的形式。其特征性病理学包括细胞外淀粉样蛋白斑块，该斑块是由于从淀粉样前体蛋白（APP）释放的淀粉样β肽（Aβ）的异常清除和/或产生增加而形成的。[1，2]金属离子，特别是Cu+/2+和Zn 2+，还有Fe 2 +/3+，参与了与Aβ病理学相关的两个过程：肽聚集和活性氧（ROS）的形成。[3]It推测APP和Aβ可能在铜稳态中发挥正常作用。[4，5]体外研究还表明，Aβ可以通过淬灭自由基和/或螯合铜来发挥抗氧化剂的作用。[6，7]然而，其他证据表明，Aβ-Cu复合物是促氧化剂，直接导致神经毒性。[8]在体外，Aβ在铜或铁和还原剂如抗坏血酸盐的存在下产生H2 O2，[9-11]其随后可与还原的金属离子反应以经由芬顿反应产生OHC [方程式11]。①]。[12，13]金属介导的H2 O2生成出现在体外Aβ聚集的早期阶段，[10，11]这支持了可溶性Aβ-Cu物质负责氧化损伤的观点，氧化损伤是阿尔茨海默病中最早的病理事件之一。[14]此外，铜已被证明可增强原代皮层神经元中的Aβ毒性。[9，10，15]与Cu 2+一样，Zn 2+也在体外促进Aβ聚集，但Zn诱导的聚集可能具有神经保护作用。[第16至18页]
Alzheimer’s is a progressive and fatal brain disease that is the most common form of dementia. Its characteristic pathology includes extracellular amyloid plaques that form as a result of abnormal clearance and/or increased production of amyloid-β peptides (Aβ) that are released from the amyloid precursor protein (APP).[1, 2] Metal ions, particularly Cu+/2+ and Zn2+, but also Fe2+/3+, have been implicated in two processes related to Aβ pathology: peptide aggregation and formation of reactive oxygen species (ROS).[3]It is speculated that both APP and Aβ might have normal roles in copper homeostasis.[4, 5] It has also been shown in vitro that Aβ can act as an antioxidant by quenching free radicals and/or by chelating copper.[6, 7] Other evidence, however, suggests that Aβ–Cu complexes are pro-oxidant and directly culpable of neurotoxicity.[8] In vitro, Aβ in the presence of copper or iron and reducing agents like ascorbate produces H2O2,[9–11] which can subsequently react with the reduced metal ions to produce OHC via the Fenton reaction [Eq.(1)].[12, 13] Metal-mediated H2O2 generation appears at an early stage during in vitro Aβ aggregation,[10, 11] which supports the notion that soluble Aβ–Cu species are responsible for the oxidative damage that is one of the earliest pathological events in Alzheimer’s disease.[14] Furthermore, copper has been shown to intensify Aβ toxicity in primary cortical neurons.[9, 10, 15] Like Cu2+, Zn2+ also promotes Aβ aggregation in vitro, but the Zn-induced aggregates could be neuroprotective.[16–18]
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影响因子：
15
作者：
Charkoudian, Louise K.;Pham, David M.;Franz, Katherine J.
通讯作者：
Franz, Katherine J.
影响因子：
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影响因子：
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作者：
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影响因子：
3.2
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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