2. Academic Validation
  3. Hepta-Histidine Inhibits Tau Aggregation

Hepta-Histidine Inhibits Tau Aggregation

  • ACS Chem Neurosci. 2021 Aug 18;12(16):3015-3027. doi: 10.1021/acschemneuro.1c00164.
Kanoh Kondo 1,  Teikichi Ikura 2,  Hikari Tanaka 1,  Kyota Fujita 1,  Sumire Takayama 1,  Yuki Yoshioka 1,  Kazuhiko Tagawa 1,  Hidenori Homma 1,  Su Liu 3,  Ryosuke Kawasaki 3,  Yong Huang 1,  Nobutoshi Ito 2,  Shin-Ichi Tate 3,  Hitoshi Okazawa 1
Affiliations

Affiliations

  • 1 Department of Neuropathology, Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
  • 2 Department of Structural Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8510 Tokyo, Japan.
  • 3 Department of Mathematical and Life Sciences, Graduate School for Integrated Sciences for Life, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan.
PMID: 34319089 DOI: 10.1021/acschemneuro.1c00164
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).

Keywords

Hepta-histidine; TAT; aggregation; neurodegenerative diseases; tau.

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