National Center for Nanoscience and Technology, Beijing 100190, China.
ACS Nano. 2011 Jul 26;5(7):6001-7. doi: 10.1021/nn201773x. Epub 2011 Jun 23.
The pathogenesis of many neurodegenerative diseases is associated with different types of aggregates of amyloidogenic peptides, including senile plaques, fibrils, protofibrils, and oligomers. It is therefore valuable to explore diversity of approaches toward reducing the cytotoxicity of amyloidogenic peptides by modulating aggregation behaviors. Herein we report an approach toward reducing the neuronal cytotoxicity of amyloidogenic peptides by accelerating the aggregation process, which is different from prevalent methods via inhibiting the aggregation of peptides. The pyridyl derivatives behave like chaperones to dramatically change the assembling characteristics of the peptides via strong hydrogen bond formation with C-termini of amyloid β (Aβ) peptides, which is revealed by using scanning probe microscopy. The light scattering experiments demonstrated the effect of the chaperone-like molecules on accelerating the aggregation process of Aβ peptides, accompanied by the reduced neuronal cytotoxicity of amyloidogenic peptides. These results would give rise to a complementary approach for modulating biological effects of the aggregates of amyloidogenic peptides.
许多神经退行性疾病的发病机制与淀粉样肽的不同类型聚集物有关，包括老年斑、纤维、原纤维和低聚物。因此，通过调节聚集行为来探索降低淀粉样肽细胞毒性的多样性方法是有价值的。本文报道了一种通过加速聚集过程来降低淀粉样肽神经毒性的方法，这与通过抑制肽聚集来降低淀粉样肽神经毒性的常见方法不同。吡啶衍生物通过与淀粉样β（Aβ）肽的 C 末端形成强氢键，类似于分子伴侣，从而显著改变肽的组装特性，这一点通过扫描探针显微镜得到了证实。光散射实验表明，分子伴侣样分子对加速 Aβ肽的聚集过程有影响，同时降低了淀粉样肽的神经毒性。这些结果为调节淀粉样肽聚集物的生物学效应提供了一种补充方法。
