Observation of Reduced Cytotoxicity of Aggregated Amyloidogenic Peptides with Chaperone-like Molecules
Observation of Reduced Cytotoxicity of Aggregated Amyloidogenic Peptides with Chaperone-like Molecules
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DOI：
10.1021/nn201773x
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发表时间：
2011-07-01
期刊：
影响因子：
17.1
通讯作者：
Wang, Chen
中科院分区：
文献类型：
--
作者：
Liu, Lei;Zhang, Lan;Wang, Chen
许多神经退行性疾病的发病机制与淀粉样蛋白生成肽的不同类型的聚集体相关，包括老年斑、原纤维、原纤维和寡聚体。因此，探索通过调节聚集行为来降低淀粉样蛋白生成肽的细胞毒性的多种方法是有价值的。本文报道了一种通过加速聚集过程来降低淀粉样蛋白生成肽的神经细胞毒性的方法，该方法不同于目前通过抑制肽的聚集来降低神经细胞毒性的方法。吡啶衍生物的行为类似于分子伴侣，通过与淀粉样蛋白β（A β）肽的C-末端形成强氢键来显著改变肽的组装特性，这通过使用扫描探针显微镜来揭示。光散射实验证明了伴侣样分子对加速A β肽聚集过程的作用，伴随着淀粉样蛋白生成肽的神经元细胞毒性降低。这些结果将产生一个补充的方法来调节淀粉样蛋白生成肽的聚集体的生物学效应。
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 beta (A beta) 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 A beta 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.