一項(xiàng)發(fā)表在《阿爾茨海默氏病雜志》上的新的研究證實(shí)：抗氧化劑可能有助治療阿爾茨海默氏癥。
阿爾茨海默氏病（AD）是美國人死亡的第六大原因,，超過65歲近八分之一的人受阿爾茨海默氏病影響,。目前還沒有治療手段能治愈這種疾病,。然而越來越多的證據(jù)表明改變身體處理鐵和其他金屬如銅和鋅的方式可能在AD癥狀開始出現(xiàn)之前就已經(jīng)發(fā)生了變化,。一項(xiàng)新的研究表明降低血漿中的鐵的含量可能保護(hù)AD患者的腦。
在醫(yī)學(xué)及健康科學(xué)學(xué)院北達(dá)科他州大學(xué)藥理學(xué)及生理學(xué)副教授Othman Ghribi博士領(lǐng)導(dǎo)的研究小組開展的這項(xiàng)研究中,，研究人員給兔子喂食高膽固醇的飲食,，使兔子腦部積累β-淀粉樣蛋白（Aβ）的一個(gè)小蛋白斑塊。這些斑塊具有神經(jīng)元毒性,，對(duì)阿爾茨海默氏病的發(fā)生發(fā)展至關(guān)重要,。兔子tau蛋白發(fā)生了變化,，tau蛋白是神經(jīng)細(xì)胞骨架的一部分。當(dāng)這種蛋白質(zhì)被過度磷酸化后,，神經(jīng)細(xì)胞之間用電信號(hào)進(jìn)行交流的能力被削弱,。兔子在給予去鐵酮（一種鐵螯合劑）后，血漿中的鐵含量減少,，大腦中的β-淀粉樣蛋白和tau蛋白的磷酸化水平也恢復(fù)到正常水平,。
另一個(gè)在AD的退化過程，涉及生產(chǎn),，可以破壞大腦中的神經(jīng)元的活性氧（ROS）,。去鐵酮也被認(rèn)為是抑制這種活性氧損傷，造成血液中的游離鐵,，但在這項(xiàng)研究中有沒有活性氧在治療組的差異,。它出現(xiàn)在AD腦鐵坐落在錯(cuò)誤的地方 - 特別是積累中的β-淀粉樣蛋白斑的核心非常高的水平，并在此設(shè)置是非常被動(dòng),。
Ghribi博士表示：“我們的數(shù)據(jù)表明用鐵螯合劑去治療能抑制高膽固醇飲食誘導(dǎo)的AD病理,，其機(jī)制為去鐵酮減少Aβ的生成，降低tau蛋白的磷酸化水平,。但鐵螯合劑對(duì)ROS水平?jīng)]有影響,，Ghribi博士說：“這可能是高劑量的去鐵酮或去鐵酮聯(lián)合一種抗氧化劑的綜合療法可以防止活性氧的產(chǎn)生，這更充分抑制了高膽固醇飲食對(duì)AD病理的有害影響”,。（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.
