低聚物
化学
τ蛋白
生物物理学
共焦显微镜
纤维
动态光散射
蛋白质聚集
水动力半径
立体化学
生物化学
物理化学
阿尔茨海默病
纳米技术
材料科学
有机化学
水溶液
纳米颗粒
病理
细胞生物学
生物
疾病
医学
胶束
作者
Arpan Pradhan,Satyendra Mishra,Avadhesha Surolia,Dulal Panda
标识
DOI:10.1021/acschemneuro.1c00098
摘要
The pathological aggregation of tau is one of the major contributing factors for several neurodegenerative tauopathies, including Alzheimer's disease. Here, we report that C1, a synthetic derivative of curcumin, strongly inhibited both the aggregation and filament formation of purified tau and protected neuroblastoma cells from the deleterious effects of the tau oligomers. Using confocal microscopy, C1 was found to reduce both the size and number of the tau droplets and increased the critical concentration of tau required for the droplet formation in vitro indicating that C1 suppressed the liquid–liquid phase separation of tau. C1 inhibited the aggregation of tau with a half-maximal inhibitory concentration of 1.5 ± 0.1 μM. An analysis of the aggregation kinetics data indicated that C1 strongly reduced the initial rate of the aggregation of tau. A dot blot analysis using tau-oligomer-specific antibody indicated that C1 inhibited the oligomerization of tau. Furthermore, dynamic light scattering experiments suggested that C1 strongly reduced the mean diameter of the tau oligomers. Atomic force microscopy experiments showed that C1 treatment reduced both the size and number of tau oligomers, suppressed the transition of tau oligomers into filaments, and also disintegrated preformed tau filaments. Also, the binding interaction of C1 with tau was monitored using absorbance and fluorescence spectroscopy. C1 bound to Y310W-tau with a dissociation constant of 2.0 ± 0.5 μM. The findings suggested that C1 is a potent inhibitor of tau aggregation and provided insights into the inhibitory mechanism of C1 on the oligomerization and fibril formation of tau.
科研通智能强力驱动
Strongly Powered by AbleSci AI