β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE

DOI Web Site 被引用文献128件
  • Robert Vassar
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Brian D. Bennett
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Safura Babu-Khan
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Steve Kahn
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Elizabeth A. Mendiaz
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Paul Denis
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • David B. Teplow
    Department of Neurology, Harvard Medical School, and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, 02115, USA.
  • Sandra Ross
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Patricia Amarante
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Richard Loeloff
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Yi Luo
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Seth Fisher
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Janis Fuller
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Steven Edenson
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Jackson Lile
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Mark A. Jarosinski
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Anja Leona Biere
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Eileen Curran
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Teresa Burgess
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Jean-Claude Louis
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Frank Collins
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • James Treanor
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Gary Rogers
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.
  • Martin Citron
    Amgen, Inc., One Amgen Center Drive, M/S 29-2-B, Thousand Oaks, CA 91320–1799, USA.

抄録

<jats:p>Cerebral deposition of amyloid β peptide (Aβ) is an early and critical feature of Alzheimer's disease. Aβ generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: β-secretase and γ-secretase. These proteases are prime therapeutic targets. A transmembrane aspartic protease with all the known characteristics of β-secretase was cloned and characterized. Overexpression of this protease, termed BACE (for beta-site APP-cleaving enzyme) increased the amount of β-secretase cleavage products, and these were cleaved exactly and only at known β-secretase positions. Antisense inhibition of endogenous BACE messenger RNA decreased the amount of β-secretase cleavage products, and purified BACE protein cleaved APP-derived substrates with the same sequence specificity as β-secretase. Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for β-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease.</jats:p>

収録刊行物

  • Science

    Science 286 (5440), 735-741, 1999-10-22

    American Association for the Advancement of Science (AAAS)

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