Host: The Japanese Pharmacological Society
Name : The 97th Annual Meeting of the Japanese Pharmacological Society
Number : 97
Location : [in Japanese]
Date : December 14, 2023 - December 16, 2023
TAR DNA-binding protein (TDP-43) consists of 414 amino acids and is a protein with functions related to RNA metabolism, such as mRNA production and transport of mature mRNA to the cytoplasm. On the other hand, TDP-43 has been shown to form amyloid due to abnormal aggregation in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, suggesting that abnormal TDP-43 propagates between cells in these diseases and causes lesions to spread to the surrounding area. However, the mechanism of this abnormal aggregation has not been elucidated, and early diagnostic and therapeutic methods have not been established. In this study, we focused on the Real-time Quaking Induced Conversion Reaction (RT-QuIC) method, an early diagnosis method that has been developed for other neurodegenerative diseases such as prion diseases and Parkinson's disease, and investigated the development of the TDP-43 RT-QuIC method.
First, recombinant TDP-43 protein was purified and seeded in vitro. The seed was used to study the optimal conditions by changing the pH and additives of the solution. Several recombinant TDP-43 mutants were also purified and used in the experiments. As a result, we identified suitable mutants of His-tagged TDP-43 and additives which increased the detection capacity, and successfully detected 50 fg of seed. Thus, the development of the TDP-43 RT-QuIC method is progressing steadily, and we hope to enable detection in biological samples in the future, ultimately aiming for clinical application.
