摘要
已有的研究表明石榴汁及提取物对阿尔茨海默病( AD )有神经保护作用,但在动物模型身上的数据有限。在此,我们研究了一个标准的石榴提取物(PE)在中老年AD转基因动物模型( R1.40 )身上对AD病理的影响。月龄为24-30的小鼠连续三周每日饲喂PE(100和200mg / kg)和对照组溶液,并在Morris水迷宫和Y迷宫改进的空间进行长期评价工作记忆功能。在脑组织中测定皮质淀粉样蛋白β前体蛋白(APP)和淀粉状蛋白β( Aβ)的水平,以及其他AD相关的生物标志物。PE没有改善小鼠的认知能力,但改变Aβ42和Aβ40肽水平和比率,有利于降低AD发病机制。进一步的分析表明,这种逆转可能是γ分泌酶的活性修饰的结果,这个酶参与这些Aβ亚型的产生。我们的研究结果证明了一个石榴提取物在老年AD动物模型中的特殊的抗淀粉样蛋白形成的机制。
关键词: 阿尔茨海默病,β淀粉样蛋白,γ分泌,多酚,石榴
Current Alzheimer Research
Title:Pomegranate Extract Modulates Processing of Amyloid-β Precursor Protein in an Aged Alzheimer`s Disease Animal Model
Volume: 11 Issue: 9
Author(s): Aseef H. Ahmed, Gehad M. Subaiea, Aseel Eid, Liya Li, Navindra P. Seeram and Nasser H. Zawia
Affiliation:
关键词: 阿尔茨海默病,β淀粉样蛋白,γ分泌,多酚,石榴
摘要: Accumulating research supports the neuroprotective effects of pomegranate (Punica granatum) juice and extracts against Alzheimer’s disease (AD) but there is limited data available in animal models. Here we investigated the effects of a standardized pomegranate extract (PE) on AD pathology in an aged transgenic AD animal model (R1.40).The mice (age 24-30 months) received either PE (at 100 and 200 mg/kg) or a control solution daily for three weeks, and were evaluated in the Morris water maze and the Y-maze for improvements in spatial long-term and working memory functions. Cortical amyloid-β precursor protein (APP) and amyloid-β (Aβ) levels, along with other relevant biomarkers for AD, were measured in brain tissues. PE did not improve cognitive performance of the mice, but altered levels and ratio of the Aβ42 and Aβ40 peptides which would favor a diminution in AD pathogenesis. Further analysis revealed that this reversal could be the product of the modification of γ-secretase enzyme activity, the enzyme involved in the generation of these Aβ isoforms. Our findings support a specific anti-amyloidogenic mechanism of a pomegranate extract in this aged AD animal model.
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Ahmed H. Aseef, Subaiea M. Gehad, Eid Aseel, Li Liya, Seeram P. Navindra and Zawia H. Nasser, Pomegranate Extract Modulates Processing of Amyloid-β Precursor Protein in an Aged Alzheimer`s Disease Animal Model, Current Alzheimer Research 2014; 11 (9) . https://dx.doi.org/10.2174/1567205011666141001115348
DOI https://dx.doi.org/10.2174/1567205011666141001115348 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
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