Institute of Human Nutrition and Food Science, Christian-Albrechts-University Kiel, Hermann-Rodewald-Strasse 6-8, 24118, Kiel, Germany,
Genes Nutr. 2014 May;9(3):397. doi: 10.1007/s12263-014-0397-3. Epub 2014 Mar 27.
Curcumin from Curcuma longa may exert putative neuroprotective properties in the brain. Impaired mitochondrial function is implicated in Alzheimer's disease and the presence of the apolipoprotein (APO) E4 genotype, which is a risk factor for late-onset Alzheimer's disease, may aggravate mitochondrial malfunction. Here, we report that in the brain of 16-month-old APOE4-targeted replacement mice, adenosine triphosphate (ATP) concentrations were significantly lower than in APOE3 mice. A 3-month dietary supplementation of 0.2 % curcumin numerically increased ATP concentrations in APOE3 and significantly in APOE4 mice compared to the respective controls. Curcumin significantly induced the transcription of peroxisome proliferator-activated receptor (PPAR) γ and mitochondrial transcription factor A (TFAM) in APOE3, but not in APOE4 mice. Moreover, PPARγ coactivator (PGC)-1α and guanine-adenine repeat binding protein α (GABPa) mRNA was only increased in APOE3 mice. Consistent with these observations, protein expression of mitochondrial respiratory complexes, especially of complex IV, also appeared to be increased in APOE3 mice. In conclusion, we provide evidence that curcumin affects mitochondrial function and gene and protein expression in the murine brain despite its low bioavailability and carriers of the Alzheimer's disease-risk genotype APOE4 may be less responsive to dietary curcumin than APOE3 carriers.
姜黄素可能对大脑具有潜在的神经保护作用。受损的线粒体功能与阿尔茨海默病有关，载脂蛋白（APO）E4 基因型是阿尔茨海默病发病晚的一个危险因素，它可能会加重线粒体功能障碍。在这里，我们报告说，在 16 个月大的 APOE4 靶向替换小鼠的大脑中，三磷酸腺苷（ATP）浓度明显低于 APOE3 小鼠。3 个月的 0.2%姜黄素饮食补充使 APOE3 和 APOE4 小鼠的 ATP 浓度与各自的对照组相比数值增加，而 APOE4 小鼠的 ATP 浓度显著增加。姜黄素显著诱导 APOE3 中过氧化物酶体增殖物激活受体（PPAR）γ 和线粒体转录因子 A（TFAM）的转录，但对 APOE4 小鼠没有影响。此外，只有在 APOE3 小鼠中，过氧化物酶体增殖物激活受体γ共激活因子（PGC）-1α和鸟嘌呤-腺嘌呤重复结合蛋白α（GABPa）mRNA 才增加。与这些观察结果一致的是，线粒体呼吸复合物的蛋白质表达，特别是复合物 IV，似乎也在 APOE3 小鼠中增加。总之，我们提供的证据表明，尽管姜黄素的生物利用度低，且携带阿尔茨海默病风险基因型 APOE4 的个体对饮食姜黄素的反应可能不如 APOE3 携带者敏感，但它会影响小鼠大脑中的线粒体功能以及基因和蛋白质表达。
