Funtan Sebastian, Evgrafova Zhanna, Adler Juliane, Huster Daniel, Binder Wolfgang H
Faculty of Natural Science II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, D-06120 Halle (Saale), Germany.
Institute for Medical Physics and Biophysics, Leipzig University, Härtelstraße 16-18, D-04107 Leipzig, Germany.
Polymers (Basel). 2016 May 2;8(5):178. doi: 10.3390/polym8050178.
The formation of amyloid fibrils is considered to be one of the main causes for many neurodegenerative diseases, such as Alzheimer's, Parkinson's or Huntington's disease. Current knowledge suggests that amyloid-aggregation represents a nucleation-dependent aggregation process , where a sigmoidal growth phase follows an induction period. Here, we studied the fibrillation of amyloid β 1-40 (Aβ) in the presence of thermoresponsive polymers, expected to alter the Aβ fibrillation kinetics due to their lower critical solution behavior. To probe the influence of molecular weight and the end groups of the polymer on its lower critical solution temperature (LCST), also considering its concentration dependence in the presence of buffer-salts needed for the aggregation studies of the amyloids, poly(oxazolines) (POx) with LCSTs ranging from 14.2⁻49.8 °C and poly(methoxy di(ethylene glycol)acrylates) with LCSTs ranging from 34.4⁻52.7 °C were synthesized. The two different polymers allowed the comparison of the influence of different molecular structures onto the fibrillation process. Mixtures of Aβ with these polymers in varying concentrations were studied via time-dependent measurements of the thioflavin T (ThT) fluorescence. The studies revealed that amyloid fibrillation was accelerated in, accompanied by an extension of the lag phase of Aβ fibrillation from 18.3 h in the absence to 19.3 h in the presence of the poly(methoxy di(ethylene glycol)acrylate) (3600 g/mol).
淀粉样纤维的形成被认为是许多神经退行性疾病的主要原因之一，如阿尔茨海默病、帕金森病或亨廷顿病。目前的知识表明，淀粉样聚集是一个依赖成核的聚集过程，其中S形生长阶段跟随诱导期。在此，我们研究了在热响应性聚合物存在下淀粉样β 1-40（Aβ）的纤维化，预期由于其较低的临界溶解行为会改变Aβ纤维化动力学。为了探究聚合物的分子量和端基对其较低临界溶解温度（LCST）的影响，同时考虑到其在淀粉样蛋白聚集研究所需的缓冲盐存在下的浓度依赖性，合成了LCST范围为14.2⁻49.8 °C的聚恶唑啉（POx）和LCST范围为34.4⁻52.7 °C的聚（甲氧基二（乙二醇）丙烯酸酯）。这两种不同的聚合物使得能够比较不同分子结构对纤维化过程的影响。通过硫黄素T（ThT）荧光的时间依赖性测量研究了Aβ与这些不同浓度聚合物的混合物。研究表明，在聚（甲氧基二（乙二醇）丙烯酸酯）（3600 g/mol）存在下，淀粉样纤维化加速，同时Aβ纤维化的延迟期从不存在时的18.3小时延长至存在时的19.3小时。
