PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo

  • PLoS One. 2015 Feb 6;10(2):e0117511. doi: 10.1371/journal.pone.0117511.
Michiaki Okuda  1 ,  Ichiro Hijikuro  2 ,  Yuki Fujita  1 ,  Xiaofeng Wu  3 ,  Shinichi Nakayama  4 ,  Yoko Sakata  4 ,  Yuji Noguchi  4 ,  Makoto Ogo  5 ,  Shigeru Akasofu  5 ,  Yoshimasa Ito  5 ,  Yoshiyuki Soeda  6 ,  Nobuhiko Tsuchiya  7 ,  Naoki Tanaka  7 ,  Takashi Takahashi  8 ,  Hachiro Sugimoto  1
Affiliations
  • 1. Pharma Eight Co., Ltd., Kyoto, Japan; Graduate School of Brain Science, Doshisha University, Kyoto, Japan.
  • 2. ChemGenesis Inc., Tokyo, Japan.
  • 3. Key Lab of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 4. Pharma Eight Co., Ltd., Kyoto, Japan.
  • 5. Tsukuba Research Laboratories, Eisai Co., Ltd., Tsukuba, Japan.
  • 6. Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
  • 7. Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto, Japan.
  • 8. Natural Product Chemistry & Pharmaceutical Research Center, Yokohama College of Pharmacy, Yokohama, Japan.
PMID: 25659102 DOI: 10.1371/journal.pone.0117511
Abstract

In tauopathies, a neural microtubule-associated protein tau (MAPT) is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies.

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