Iron accumulation in Alzheimer disease is a source of redox-generated free radicals
Iron accumulation in Alzheimer disease is a source of redox-generated free radicals
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DOI：
10.1073/pnas.94.18.9866
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发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
Perry, G
中科院分区：
文献类型：
--
作者：
Smith, MA;Harris, PLR;Perry, G
自由基的损伤已经在阿尔茨海默病的易感神经元群体中得到证实。在本研究中，我们调查了铁是否可能是阿尔茨海默病中自由基的来源，铁是由Fenton反应与H2O2产生的高活性羟基自由基的有效来源。我们发现，使用一种改进的组织化学技术，依赖于混合价铁配合物的形成。氧化还原活性铁与老年斑和神经原纤维缠结有关，这是该疾病的病理标志病变。这种病变相关的铁能够参与原位氧化，并容易催化h2o2依赖性氧化。此外，使用去铁胺可以完全去除铁，之后铁可以被反射到病变处。铁结合位点的特征表明，铁的结合依赖于可用的组氨酸残基和蛋白质构象。综上所述，这些发现表明铁的积累可能是阿尔茨海默病氧化损伤的重要因素。
Damage from free radicals has been demonstrated in susceptible neuronal populations in cases of Alzheimer disease, In this study, we investigated whether iron, a potent source of the highly reactive hydroxyl radical that is generated by the Fenton reaction with H2O2, might contribute to the source of radicals in Alzheimer disease, We found, using a modified histochemical technique that relies on the formation of mixed valence iron complexes, that redox-active iron is associated with the senile plaques and neurofibrillary tangles-the pathological hallmark lesions of this disease, This lesion-associated iron is able to participate in in situ oxidation and readily catalyzes an H2O2-dependent oxidation. Furthermore, removal of iron was completely effected using deferoxamine, after which iron could be rebound to the lesions, Characterization of the iron-binding site suggests that binding is dependent on available histidine residues and on protein conformation, Taken together, these findings indicate that iron accumulation could be an important contributor toward the oxidative damage of Alzheimer disease.