纳米孔
蛋白质聚集
突变体
生物物理学
纤维
淀粉样蛋白(真菌学)
单体
化学
突变
淀粉样纤维
淀粉样β
材料科学
聚合物
纳米技术
生物
生物化学
疾病
基因
有机化学
无机化学
病理
医学
作者
Nicoletta Giamblanco,Yann Fichou,Jean-Marc Janot,Emmanuel Balanzat,Songi Han,Sebastien Balme
出处
期刊:ACS Sensors
[American Chemical Society]
日期:2020-03-27
卷期号:5 (4): 1158-1167
被引量:25
标识
DOI:10.1021/acssensors.0c00193
摘要
Protein aggregation is involved in many diseases, including Parkinson’s and Alzheimer’s. The latter is characterized by intraneuronal deposition of amyloid aggregates composed of the tau protein. Although large and insoluble aggregates are typically found in affected brains, intermediate soluble oligomers are thought to represent crucial species for toxicity and spreading. Nanopore sensors constitute an emerging technology that allows the detection of the size and populations of molecular assembly present in a sample. Here, we employed conical nanopores to obtain the particle distributions during tau aggregation. We identified three distinct populations, monomers, oligomers, and fibrils, which we could quantify along the aggregation process. By comparing tau wild type with a mutant carrying the disease-associated P301L mutation, we showed that the latter mutation promotes the formation of oligomers. We furthermore highlighted that the P301L mutation promotes fibril breakage. This work demonstrates that conical nanopore is a powerful tool to measure and quantify transient protein aggregate intermediates.
科研通智能强力驱动
Strongly Powered by AbleSci AI