Protein-Based Biosensor for Screening of Tau Aggregation Inhibitors, a Pharmaceutical Application

摘要

Aggregation of tau proteins underlies several neurodegenerative diseases, notably Alzheimer's disease (AD). Protein aggregation is a complex multi-step process where normal soluble proteins self-assemble in an ordered fashion into higher order conglomerates of low solubility. Experimental evidence suggests that not only the large tau aggregates, known as neurofibrillary tangles (NFTs), are involved in neuronal death, but also small tau oligomers are more likely contributed to the neuronal toxicity. While in the recent years substantial progress has been made in the design of drugs that interfere with tau aggregation, there is a lack of methods available that allow rapid screening of potential drug candidates which is critical for the future successful clinical trial. The heterogeneous nature of protein aggregation is the key challenge for testing the aggregation inhibition.