JAD：抗氧化剂可能对阿尔茨海默氏症有效

一项发表在《阿尔茨海默氏病杂志》上的新的研究证实：抗氧化剂可能有助治疗阿尔茨海默氏症。

阿尔茨海默氏病（AD）是美国人死亡的第六大原因，超过65岁近八分之一的人受阿尔茨海默氏病影响。目前还没有治疗手段能治愈这种疾病。然而越来越多的证据表明改变身体处理铁和其他金属如铜和锌的方式可能在AD症状开始出现之前就已经发生了变化。一项新的研究表明降低血浆中的铁的含量可能保护AD患者的脑。

在医学及健康科学学院北达科他州大学药理学及生理学副教授Othman Ghribi博士领导的研究小组开展的这项研究中，研究人员给兔子喂食高胆固醇的饮食，使兔子脑部积累β-淀粉样蛋白（Aβ）的一个小蛋白斑块。这些斑块具有神经元毒性，对阿尔茨海默氏病的发生发展至关重要。兔子tau蛋白发生了变化，tau蛋白是神经细胞骨架的一部分。当这种蛋白质被过度磷酸化后，神经细胞之间用电信号进行交流的能力被削弱。兔子在给予去铁酮（一种铁螯合剂）后，血浆中的铁含量减少，大脑中的β-淀粉样蛋白和tau蛋白的磷酸化水平也恢复到正常水平。

另一个在AD的退化过程，涉及生产，可以破坏大脑中的神经元的活性氧（ROS）。去铁酮也被认为是抑制这种活性氧损伤，造成血液中的游离铁，但在这项研究中有没有活性氧在治疗组的差异。它出现在AD脑铁坐落在错误的地方 - 特别是积累中的β-淀粉样蛋白斑的核心非常高的水平，并在此设置是非常被动。

Ghribi博士表示：“我们的数据表明用铁螯合剂去治疗能抑制高胆固醇饮食诱导的AD病理，其机制为去铁酮减少Aβ的生成，降低tau蛋白的磷酸化水平。但铁螯合剂对ROS水平没有影响，Ghribi博士说：“这可能是高剂量的去铁酮或去铁酮联合一种抗氧化剂的综合疗法可以防止活性氧的产生，这更充分抑制了高胆固醇饮食对AD病理的有害影响”。（生物谷：Bioon）

doi:10.3233/JAD-2012-111346
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Deferiprone Reduces Amyloid and Tau Phosphorylation Levels but not Reactive Oxygen Species Generation in Hippocampus of Rabbits Fed a Cholesterol-Enriched Diet.

Jaya R.P. Prasanthi, Matthew Schrag, Bhanu Dasari, Gurdeep Marwarha, Wolff M. Kirsch and Othman Ghribi.

Accumulation of amyloid-β (Aβ) peptide and the hyperphosphorylation of tau protein are major hallmarks of Alzheimer's disease (AD). The causes of AD are not well known but a number of environmental and dietary factors are suggested to increase the risk of developing AD. Additionally, altered metabolism of iron may have a role in the pathogenesis of AD. We have previously demonstrated that cholesterol-enriched diet causes AD-like pathology with iron deposition in rabbit brain. However, the extent to which chelation of iron protects against this pathology has not been determined. In this study, we administered the iron chelator deferiprone in drinking water to rabbits fed with a 2% cholesterol diet for 12 weeks. We found that deferiprone (both at 10 and 50 mg/kg/day) significantly decreased levels of Aβ40 and Aβ42 as well as BACE1, the enzyme that initiates cleavage of amyloid-β protein precursor to yield Aβ. Deferiprone also reduced the cholesterol diet-induced increase in phosphorylation of tau but failed to reduce reactive oxygen species generation. While deferiprone treatment was not associated with any change in brain iron levels, it was associated with a significant reduction in plasma iron and cholesterol levels. These results demonstrate that deferiprone confers important protection against hypercholesterolemia-induced AD pathology but the mechanism(s) may involve reduction in plasma iron and cholesterol levels rather than chelation of brain iron. We propose that adding an antioxidant therapy to deferiprone may be necessary to fully protect against cholesterol-enriched diet-induced AD-like pathology.