2. Academic Validation
  3. A noncompetitive BACE1 inhibitor TAK-070 ameliorates Abeta pathology and behavioral deficits in a mouse model of Alzheimer's disease

A noncompetitive BACE1 inhibitor TAK-070 ameliorates Abeta pathology and behavioral deficits in a mouse model of Alzheimer's disease

  • J Neurosci. 2010 Aug 18;30(33):11157-66. doi: 10.1523/JNEUROSCI.2884-10.2010.
Hiroaki Fukumoto 1,  Hideki Takahashi,  Naoki Tarui,  Junji Matsui,  Taisuke Tomita,  Mitsuhiro Hirode,  Masumi Sagayama,  Ryouta Maeda,  Makiko Kawamoto,  Kazuko Hirai,  Jun Terauchi,  Yasufumi Sakura,  Mitsuru Kakihana,  Kaneyoshi Kato,  Takeshi Iwatsubo,  Masaomi Miyamoto
Affiliations

Affiliation

  • 1 Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Yodogawa-ku, Osaka 532-8686, Japan. Fukumoto_Hiroaki@takeda.co.jp
PMID: 20720123 DOI: 10.1523/JNEUROSCI.2884-10.2010
Abstract

We discovered a nonpeptidic compound, TAK-070, that inhibited BACE1, a rate-limiting Protease for the generation of Abeta Peptides that are considered causative for Alzheimer's disease (AD), in a noncompetitive manner. TAK-070 bound to full-length BACE1, but not to truncated BACE1 lacking the transmembrane domain. Short-term oral administration of TAK-070 decreased the brain levels of soluble Abeta, increased that of neurotrophic sAPPalpha by approximately 20%, and normalized the behavioral impairments in cognitive tests in Tg2576 mice, an APP transgenic mouse model of AD. Six-month chronic treatment decreased cerebral Abeta deposition by approximately 60%, preserving the pharmacological efficacy on soluble Abeta and sAPPalpha levels. These results support the feasibility of BACE1 inhibition with a noncompetitive inhibitor as disease-modifying as well as symptomatic therapy for AD.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z