title: PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo.
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.
authors: Pharma Eight Co., Ltd., Kyoto, Japan; Graduate School of Brain Science, Doshisha University, Kyoto, Japan.
authors: Michiaki
authors: M
authors: Okuda
authors: ChemGenesis Inc., Tokyo, Japan.
authors: Ichiro
authors: I
authors: Hijikuro
authors: Pharma Eight Co., Ltd., Kyoto, Japan; Graduate School of Brain Science, Doshisha University, Kyoto, Japan.
authors: Yuki
authors: Y
authors: Fujita
authors: Key Lab of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors: Xiaofeng
authors: X
authors: Wu
authors: Pharma Eight Co., Ltd., Kyoto, Japan.
authors: Shinichi
authors: S
authors: Nakayama
authors: Pharma Eight Co., Ltd., Kyoto, Japan.
authors: Yoko
authors: Y
authors: Sakata
authors: Pharma Eight Co., Ltd., Kyoto, Japan.
authors: Yuji
authors: Y
authors: Noguchi
authors: Tsukuba Research Laboratories, Eisai Co., Ltd., Tsukuba, Japan.
authors: Makoto
authors: M
authors: Ogo
authors: Tsukuba Research Laboratories, Eisai Co., Ltd., Tsukuba, Japan.
authors: Shigeru
authors: S
authors: Akasofu
authors: Tsukuba Research Laboratories, Eisai Co., Ltd., Tsukuba, Japan.
authors: Yoshimasa
authors: Y
authors: Ito
authors: Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan.
authors: Yoshiyuki
authors: Y
authors: Soeda
authors: Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto, Japan.
authors: Nobuhiko
authors: N
authors: Tsuchiya
authors: Department of Biomolecular Engineering, Kyoto Institute of Technology, Kyoto, Japan.
authors: Naoki
authors: N
authors: Tanaka
authors: Natural Product Chemistry & Pharmaceutical Research Center, Yokohama College of Pharmacy, Yokohama, Japan.
authors: Takashi
authors: T
authors: Takahashi
authors: Pharma Eight Co., Ltd., Kyoto, Japan; Graduate School of Brain Science, Doshisha University, Kyoto, Japan.
authors: Hachiro
authors: H
authors: Sugimoto
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D020125:Mutation, Missense; D066263:Protein Aggregation, Pathological / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024801:Tauopathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C000596012:3-(2-(1H-indol-6-yl)ethenyl)-5-(2-(2-methoxy-4-(2-pyridylmethoxy)phenyl)ethenyl)-1H-pyrazole; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; C054369:MAPT protein, human; D011720:Pyrazoles; D016875:tau Proteins