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η-Secretase processing of APP inhibits neuronal activity in the hippocampus

Author

Listed:
  • Michael Willem

    (Biomedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Sabina Tahirovic

    (German Center for Neurodegenerative Diseases (DZNE) Munich)

  • Marc Aurel Busche

    (Technische Universität München
    Institute of Neuroscience, Technische Universität München
    Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich)

  • Saak V. Ovsepian

    (German Center for Neurodegenerative Diseases (DZNE) Munich)

  • Magda Chafai

    (Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS), Université de Nice Sophia Antipolis)

  • Scherazad Kootar

    (Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS), Université de Nice Sophia Antipolis)

  • Daniel Hornburg

    (Max Planck Institute of Biochemistry)

  • Lewis D. B. Evans

    (Gurdon Institute, University of Cambridge)

  • Steven Moore

    (Gurdon Institute, University of Cambridge)

  • Anna Daria

    (Biomedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Heike Hampel

    (Biomedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Veronika Müller

    (Biomedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Camilla Giudici

    (Biomedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Brigitte Nuscher

    (Biomedical Center (BMC), Ludwig-Maximilians-University Munich)

  • Andrea Wenninger-Weinzierl

    (German Center for Neurodegenerative Diseases (DZNE) Munich)

  • Elisabeth Kremmer

    (German Center for Neurodegenerative Diseases (DZNE) Munich
    Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich
    Institute of Molecular Immunology, German Research Center for Environmental Health)

  • Michael T. Heneka

    (Clinical Neuroscience Unit, University of Bonn
    German Center for Neurodegenerative Diseases (DZNE) Bonn)

  • Dietmar R. Thal

    (Institute of Pathology - Laboratory for Neuropathology, University of Ulm)

  • Vilmantas Giedraitis

    (Uppsala University)

  • Lars Lannfelt

    (Uppsala University)

  • Ulrike Müller

    (Institute for Pharmacy and Molecular Biotechnology IPMB, Functional Genomics, University of Heidelberg)

  • Frederick J. Livesey

    (Gurdon Institute, University of Cambridge)

  • Felix Meissner

    (Max Planck Institute of Biochemistry)

  • Jochen Herms

    (German Center for Neurodegenerative Diseases (DZNE) Munich)

  • Arthur Konnerth

    (Institute of Neuroscience, Technische Universität München
    Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich)

  • Hélène Marie

    (Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS), Université de Nice Sophia Antipolis)

  • Christian Haass

    (Biomedical Center (BMC), Ludwig-Maximilians-University Munich
    German Center for Neurodegenerative Diseases (DZNE) Munich
    Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-University Munich)

Abstract

A new pathway for the processing of β-amyloid precursor protein (APP) is described in which η-secretase activity, in part mediated by the MT5-MMP metalloproteinase, cleaves APP, and further processing by ADAM10 and BACE1 generates proteolytic fragments capable of inhibiting long-term potentiation in the hippocampus.

Suggested Citation

  • Michael Willem & Sabina Tahirovic & Marc Aurel Busche & Saak V. Ovsepian & Magda Chafai & Scherazad Kootar & Daniel Hornburg & Lewis D. B. Evans & Steven Moore & Anna Daria & Heike Hampel & Veronika M, 2015. "η-Secretase processing of APP inhibits neuronal activity in the hippocampus," Nature, Nature, vol. 526(7573), pages 443-447, October.
    • Handle: RePEc:nat:nature:v:526:y:2015:i:7573:d:10.1038_nature14864
    DOI: 10.1038/nature14864
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