Assarsson Anna, Linse Sara, Cabaleiro-Lago Celia
Division of Biochemistry and Structural Biology, Lund University , P.O. Box 124, SE 221 00 Lund, Sweden.
Langmuir. 2014 Jul 29;30(29):8812-8. doi: 10.1021/la501414j. Epub 2014 Jul 14.
The fibril formation of the neurodegenerative peptide amyloid β (Aβ42) is sensitive to solution conditions, and several proteins and peptides have been found to retard the process. Aβ42 fibril formation was followed with ThT fluorescence in the presence of polyamino acids (poly-glutamic acid, poly-lysine, and poly-threonine) and other polymers (poly(acrylic acid), poly(ethylenimine), and poly(diallyldimethylammonium chloride). An accelerating effect on the Aβ42 aggregation process is observed from all positively charged polymers, while no effect is seen from the negative or neutral polymers. The accelerating effect is dependent on the concentration of positive polymer in a highly reproducible manner. Acceleration is observed from a 1:500 polymer to Aβ42 weight ratio and up. Polyamino acids and the other polymers exert quantitatively the same effect at the same concentrations based on weight. Fibrils are formed in all cases as verified by transmission electron microscopy. The concentrations of polymers required for acceleration are too low to affect the Aβ42 aggregation process through increased ionic strength or molecular crowding effects. Instead, the acceleration seems to arise from the locally increased Aβ42 concentration near the polymers, which favors association and affects the electrostatic environment of the peptide.
神经退行性肽β淀粉样蛋白（Aβ42）的纤维形成对溶液条件敏感，并且已发现几种蛋白质和肽可延缓该过程。在存在聚氨基酸（聚谷氨酸、聚赖氨酸和聚苏氨酸）和其他聚合物（聚丙烯酸、聚乙烯亚胺和聚二烯丙基二甲基氯化铵）的情况下，用硫黄素T荧光跟踪Aβ42纤维的形成。所有带正电荷的聚合物均对Aβ42聚集过程有加速作用，而带负电荷或中性的聚合物则无此作用。加速作用以高度可重复的方式依赖于正聚合物的浓度。从聚合物与Aβ42的重量比为1:500及以上时可观察到加速作用。聚氨基酸和其他聚合物在相同重量浓度下具有定量相同的作用。通过透射电子显微镜验证，在所有情况下均形成了纤维。加速所需的聚合物浓度过低，无法通过增加离子强度或分子拥挤效应来影响Aβ42聚集过程。相反，加速作用似乎源于聚合物附近局部Aβ42浓度的增加，这有利于缔合并影响肽的静电环境。
