Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic.
Soft Matter. 2021 Feb 19;17(6):1628-1641. doi: 10.1039/d0sm01884h.
We investigated the influence of glycogen (GG), phytoglycogen (PG), mannan (MAN) and cinnamoyl-modified GG (GG-CIN) on amyloid fibril formation. We used hen egg-white lysozyme (HEWL) as a model system and amyloid beta peptide (1-42) (Aβ1-42) as an Alzheimer's disease-relevant system. For brief detection of fibrils was used thioflavin T (ThT) fluorescence assay and the results were confirmed by transmission electron microscopy (TEM). We also deal with the interaction of polysaccharides and HEWL with isothermal titration calorimetry (ITC) and dynamic light scattering (DLS). We found that all polysaccharides accelerated the formation of amyloid fibrils from both HEWL and Aβ1-42. At high but physiologically relevant concentrations of GG, amyloid fibril formation was extremely accelerated for HEWL. Therefore, on the basis of the herein presented in vitro data, we hypothesize, that dietary d-glucose intake may influence amyloid fibril formation not only by influencing regulatory pathways, but also by direct glycogen-amyloid precursor protein molecular interaction, as glycogen levels in tissues are highly dependent on d-glucose intake.
我们研究了糖原（GG）、植物糖原（PG）、甘露聚糖（MAN）和肉桂酰修饰的 GG（GG-CIN）对淀粉样纤维形成的影响。我们使用鸡卵清白溶菌酶（HEWL）作为模型系统，以及阿尔茨海默病相关的淀粉样β肽（1-42）（Aβ1-42）作为模型系统。为了简要检测纤维，我们使用了硫黄素 T（ThT）荧光测定法，并通过透射电子显微镜（TEM）确认了结果。我们还通过等温滴定量热法（ITC）和动态光散射（DLS）处理了多糖和 HEWL 的相互作用。我们发现所有多糖都加速了 HEWL 和 Aβ1-42 形成淀粉样纤维。在高但生理相关浓度的 GG 下，HEWL 的淀粉样纤维形成被极快地加速。因此，基于本文提出的体外数据，我们假设，膳食 d-葡萄糖的摄入不仅可以通过影响调节途径，还可以通过直接的糖原-淀粉样前体蛋白分子相互作用来影响淀粉样纤维形成，因为组织中的糖原水平高度依赖于 d-葡萄糖的摄入。
