My NCBISign In

Display Settings:

Format

Send to:

Choose Destination
    J Neurosci. 2010 Aug 18;30(33):11157-66.

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

    Fukumoto H, Takahashi H, Tarui N, Matsui J, Tomita T, Hirode M, Sagayama M, Maeda R, Kawamoto M, Hirai K, Terauchi J, Sakura Y, Kakihana M, Kato K, Iwatsubo T, Miyamoto M.

    Source

    Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Yodogawa-ku, Osaka 532-8686, Japan. Fukumoto_Hiroaki@takeda.co.jp

    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.

    PMID:
    20720123
    [PubMed - indexed for MEDLINE]
    Free full text

    MeSH Terms, Substances

    MeSH Terms

    Substances

    LinkOut - more resources

    Full Text Sources

    Other Literature Sources

    Medical

      Supplemental Content

      Click here to read

      Related citations

      See reviews... See all...

      Cited by 2 PubMed Central articles

      Related information

      • Related Citations
        Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
      • Substance (MeSH Keyword)
        PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
      • Cited in PMC
        Full-text articles in the PubMed Central Database that cite the current articles.

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...
      You are here: NCBI > Literature > PubMed
      Write to the Help Desk