Hepta-Histidine Inhibits Tau Aggregation
Kanoh Kondo, Teikichi Ikura, Hikari Tanaka, Kyota Fujita, Sumire Takayama, Yuki Yoshioka, Kazuhiko Tagawa, Hidenori Homma, Su Liu, Ryosuke Kawasaki, Yong Huang, Nobutoshi Ito, Shin‐ichi Tate, Hitoshi Okazawa
Abstract
Tau aggregation is a central hallmark of tauopathies such as frontotemporal lobar degeneration and progressive supranuclear palsy as well as of Alzheimer’s disease, and it has been a target for therapeutic development. Herein, we unexpectedly found that hepta-histidine (7H), an inhibitor of the interaction between Ku70 and Huntingtin proteins, suppresses aggregation of Tau-R3 peptides in vitro. Addition of the trans-activator of transcription (TAT) sequence (YGRKKRRQRRR) derived from the TAT protein to 7H increased its permeability into cells, and TAT-7H treatment of iPS cell-derived neurons carrying Tau or APP mutations suppressed Tau phosphorylation. These results indicate that 7H is a promising lead compound for developing anti-aggregation drugs against Tau-related neurodegenerative diseases including Alzheimer’s disease (AD).