IFM-Department of Chemistry, Linköping University, Linköping, Sweden.
PLoS One. 2012;7(2):e31424. doi: 10.1371/journal.pone.0031424. Epub 2012 Feb 13.
The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aβ toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of Aβ deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aβ deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aβ(1-42) in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aβ(1-42). Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aβ, resulting in a reduced neurotoxicity in Drosophila.
阿尔茨海默病（AD）的病理学特征是存在错误折叠和聚集的淀粉样β（Aβ）肽的细胞外沉积物和由高度磷酸化的 Tau 蛋白组成的神经元内缠结的积累。多年来，天然化合物姜黄素一直被提议作为增强清除有毒 Aβ 淀粉样蛋白的候选药物。在这项研究中，我们研究了喂食姜黄素作为药物候选物以减轻转基因果蝇中 Aβ 毒性的效力。与对照品系相比，五种不同 AD 模型基因型的寿命和运动活性显示出高达 75%的寿命和活性提高。与大多数关于姜黄素对淀粉样蛋白影响的研究不同，我们没有观察到姜黄素处理后 Aβ 沉积量的任何减少。与不同果蝇基因型中 Aβ 沉积物结合的荧光共轭寡聚噻吩 p-FTAA 的构象依赖性光谱随时间推移表明，在姜黄素处理的果蝇中，Aβ（1-42）的预纤维到纤维的转化加速。这一发现得到了重组 Aβ（1-42）体外纤化测定的支持。我们的研究表明，姜黄素通过减少 Aβ 的预纤维/寡聚体物种来促进淀粉样纤维转化，从而降低果蝇的神经毒性。
