Oxidative stress and neurodegeneration
Oxidative stress and neurodegeneration
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DOI：
10.1196/annals.1333.062
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Perry, G
中科院分区：
文献类型：
--
作者：
Moreira, PI;Smith, MA;Perry, G
氧化应激是慢性神经退行性疾病的早期反应，包括阿尔茨海默病，在这种疾病中，脆弱的神经元群体中神经元损失可能超过90%。氧化应激影响所有种类的大分子（糖、脂质、蛋白质和DNA），不可避免地导致神经元功能障碍。我们观察到，N-（羧甲基）赖氨酸（CML）是体内积累的主要晚期糖基化终产物，与其糖基化特异性前体己糖醇赖氨酸一起，在阿尔茨海默病患者的神经元中增加，特别是那些含有细胞内神经原纤维病理的患者。己糖醇-赖氨酸和CML的增加可能是由于脂质过氧化或晚期糖基化引起的，而己糖醇-赖氨酸仅仅是糖基化的产物，这表明两种不同的氧化过程在该疾病的神经病理学中协同作用。此外，使用嗅觉神经元作为实验模型，我们观察到来自阿尔茨海默病患者的神经元中糖基化产物的增加。我们的研究结果支持醛介导的修饰，与氧化自由基介导的修饰一致，是阿尔茨海默病的关键早期致病因素。
Oxidative stress is a well-studied early response in chronic neurodegenerative diseases, including Alzheimer's disease, where neuronal loss can exceed 90% in the vulnerable neuronal population. Oxidative stress affects all classes of macromolecules (sugar, lipids, proteins, and DNA), leading inevitably to neuronal dysfunction. We observed that N-(carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates in vivo, along with its glycation-specific precursor hexitol-lysine, are increased in neurons from cases of Alzheimer's disease, especially those containing intracellular neurofibrillary pathology. The increase in hexitol-lysine and CML can result from either lipid peroxidation or advanced glycation, whereas hexitol-lysine is solely a product of glycation, suggesting that two distinct oxidative processes act in concert in the neuropathology of the disease. Furthermore, using olfactory neurons as an experimental model, we observed an increase in glycation products in neurons derived from Alzheimer's disease patients. Our findings support the idea that aldehyde-mediated modifications, in concert with oxyradical-mediated modifications, are critical early pathogenic factors in Alzheimer's disease.