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@ARTICLE{Kuhn:136120,
      author       = {Kuhn, Peer-Hendrik and Wang, Huanhuan and Dislich, Bastian
                      and Colombo, Alessio and Zeitschel, Ulrike and Ellwart,
                      Joachim W and Kremmer, Elisabeth and Rossner, Steffen and
                      Lichtenthaler, Stefan},
      title        = {{ADAM}10 is the physiologically relevant, constitutive
                      alpha-secretase of the amyloid precursor protein in primary
                      neurons.},
      journal      = {The EMBO journal},
      volume       = {29},
      number       = {17},
      issn         = {0261-4189},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2020-02442},
      pages        = {3020-3032},
      year         = {2010},
      abstract     = {The amyloid precursor protein (APP) undergoes constitutive
                      shedding by a protease activity called alpha-secretase. This
                      is considered an important mechanism preventing the
                      generation of the Alzheimer's disease amyloid-beta peptide
                      (Abeta). alpha-Secretase appears to be a metalloprotease of
                      the ADAM family, but its identity remains to be established.
                      Using a novel alpha-secretase-cleavage site-specific
                      antibody, we found that RNAi-mediated knockdown of ADAM10,
                      but surprisingly not of ADAM9 or 17, completely suppressed
                      APP alpha-secretase cleavage in different cell lines and in
                      primary murine neurons. Other proteases were not able to
                      compensate for this loss of alpha-cleavage. This finding was
                      further confirmed by mass-spectrometric detection of
                      APP-cleavage fragments. Surprisingly, in different cell
                      lines, the reduction of alpha-secretase cleavage was not
                      paralleled by a corresponding increase in the
                      Abeta-generating beta-secretase cleavage, revealing that
                      both proteases do not always compete for APP as a substrate.
                      Instead, our data suggest a novel pathway for APP
                      processing, in which ADAM10 can partially compete with
                      gamma-secretase for the cleavage of a C-terminal APP
                      fragment generated by beta-secretase. We conclude that
                      ADAM10 is the physiologically relevant, constitutive
                      alpha-secretase of APP.},
      keywords     = {ADAM Proteins: metabolism / ADAM10 Protein / Amyloid
                      Precursor Protein Secretases: metabolism / Amyloid
                      beta-Protein Precursor: metabolism / Animals / Cell Line /
                      Humans / Mass Spectrometry / Membrane Proteins: metabolism /
                      Mice / Neurons: enzymology / Neurons: metabolism / Amyloid
                      beta-Protein Precursor (NLM Chemicals) / Aplp1 protein,
                      mouse (NLM Chemicals) / Membrane Proteins (NLM Chemicals) /
                      Amyloid Precursor Protein Secretases (NLM Chemicals) / ADAM
                      Proteins (NLM Chemicals) / ADAM10 Protein (NLM Chemicals) /
                      Adam10 protein, mouse (NLM Chemicals)},
      cin          = {AG Lichtenthaler},
      ddc          = {570},
      cid          = {I:(DE-2719)1110006},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:20676056},
      pmc          = {pmc:PMC2944055},
      doi          = {10.1038/emboj.2010.167},
      url          = {https://pub.dzne.de/record/136120},
}