% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Willem:138158,
      author       = {Willem, Michael and Tahirovic, Sabina and Busche, Marc
                      Aurel and Ovsepian, Saak V and Chafai, Magda and Kootar,
                      Scherazad and Hornburg, Daniel and Evans, Lewis D B and
                      Moore, Steven and Daria, Anna and Hampel, Heike and Müller,
                      Veronika and Giudici, Camilla and Nuscher, Brigitte and
                      Wenninger-Weinzierl, Andrea and Kremmer, Elisabeth and
                      Heneka, Michael T and Thal, Dietmar R and Giedraitis,
                      Vilmantas and Lannfelt, Lars and Müller, Ulrike and
                      Livesey, Frederick J and Meissner, Felix and Herms, Jochen
                      and Konnerth, Arthur and Marie, Hélène and Haass,
                      Christian},
      title        = {η-{S}ecretase processing of {APP} inhibits neuronal
                      activity in the hippocampus.},
      journal      = {Nature},
      volume       = {526},
      number       = {7573},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group65848},
      reportid     = {DZNE-2020-04480},
      pages        = {443-447},
      year         = {2015},
      abstract     = {Alzheimer disease (AD) is characterized by the accumulation
                      of amyloid plaques, which are predominantly composed of
                      amyloid-β peptide. Two principal physiological pathways
                      either prevent or promote amyloid-β generation from its
                      precursor, β-amyloid precursor protein (APP), in a
                      competitive manner. Although APP processing has been studied
                      in great detail, unknown proteolytic events seem to hinder
                      stoichiometric analyses of APP metabolism in vivo. Here we
                      describe a new physiological APP processing pathway, which
                      generates proteolytic fragments capable of inhibiting
                      neuronal activity within the hippocampus. We identify higher
                      molecular mass carboxy-terminal fragments (CTFs) of APP,
                      termed CTF-η, in addition to the long-known CTF-α and
                      CTF-β fragments generated by the α- and β-secretases
                      ADAM10 (a disintegrin and metalloproteinase 10) and BACE1
                      (β-site APP cleaving enzyme 1), respectively. CTF-η
                      generation is mediated in part by membrane-bound matrix
                      metalloproteinases such as MT5-MMP, referred to as
                      η-secretase activity. η-Secretase cleavage occurs
                      primarily at amino acids 504-505 of APP695, releasing a
                      truncated ectodomain. After shedding of this ectodomain,
                      CTF-η is further processed by ADAM10 and BACE1 to release
                      long and short Aη peptides (termed Aη-α and Aη-β). CTFs
                      produced by η-secretase are enriched in dystrophic neurites
                      in an AD mouse model and in human AD brains. Genetic and
                      pharmacological inhibition of BACE1 activity results in
                      robust accumulation of CTF-η and Aη-α. In mice treated
                      with a potent BACE1 inhibitor, hippocampal long-term
                      potentiation was reduced. Notably, when recombinant or
                      synthetic Aη-α was applied on hippocampal slices ex vivo,
                      long-term potentiation was lowered. Furthermore, in vivo
                      single-cell two-photon calcium imaging showed that
                      hippocampal neuronal activity was attenuated by Aη-α.
                      These findings not only demonstrate a major functionally
                      relevant APP processing pathway, but may also indicate
                      potential translational relevance for therapeutic strategies
                      targeting APP processing.},
      keywords     = {ADAM Proteins: metabolism / ADAM10 Protein / Alzheimer
                      Disease: enzymology / Alzheimer Disease: metabolism /
                      Amyloid Precursor Protein Secretases: antagonists $\&$
                      inhibitors / Amyloid Precursor Protein Secretases:
                      cerebrospinal fluid / Amyloid Precursor Protein Secretases:
                      deficiency / Amyloid Precursor Protein Secretases: genetics
                      / Amyloid Precursor Protein Secretases: metabolism / Amyloid
                      beta-Protein Precursor: cerebrospinal fluid / Amyloid
                      beta-Protein Precursor: chemistry / Amyloid beta-Protein
                      Precursor: genetics / Amyloid beta-Protein Precursor:
                      metabolism / Animals / Aspartic Acid Endopeptidases:
                      antagonists $\&$ inhibitors / Aspartic Acid Endopeptidases:
                      deficiency / Aspartic Acid Endopeptidases: genetics /
                      Aspartic Acid Endopeptidases: metabolism / Calcium Signaling
                      / Disease Models, Animal / Female / Hippocampus: cytology /
                      Hippocampus: enzymology / Hippocampus: physiology / Humans /
                      In Vitro Techniques / Long-Term Potentiation / Male / Matrix
                      Metalloproteinases, Membrane-Associated: deficiency / Matrix
                      Metalloproteinases, Membrane-Associated: metabolism /
                      Membrane Proteins: metabolism / Mice / Molecular Weight /
                      Neurites: enzymology / Neurites: metabolism / Neurons:
                      enzymology / Neurons: physiology / Peptide Fragments:
                      chemistry / Peptide Fragments: metabolism / Plaque, Amyloid
                      / Protein Processing, Post-Translational / Proteolysis /
                      Single-Cell Analysis / APP protein, human (NLM Chemicals) /
                      Amyloid beta-Protein Precursor (NLM Chemicals) / Membrane
                      Proteins (NLM Chemicals) / Peptide Fragments (NLM Chemicals)
                      / Amyloid Precursor Protein Secretases (NLM Chemicals) /
                      Aspartic Acid Endopeptidases (NLM Chemicals) / BACE1
                      protein, human (NLM Chemicals) / Bace1 protein, mouse (NLM
                      Chemicals) / ADAM Proteins (NLM Chemicals) / Matrix
                      Metalloproteinases, Membrane-Associated (NLM Chemicals) /
                      Mmp24 protein, mouse (NLM Chemicals) / ADAM10 Protein (NLM
                      Chemicals) / ADAM10 protein, human (NLM Chemicals)},
      cin          = {AG Tahirovic / AG Herms / AG Haass old / Ext HZM / AG
                      Heneka2},
      ddc          = {500},
      cid          = {I:(DE-2719)1140003 / I:(DE-2719)1110001 /
                      I:(DE-2719)1110007 / I:(DE-2719)5000050 /
                      I:(DE-2719)1011303},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
                      - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26322584},
      pmc          = {pmc:PMC6570618},
      doi          = {10.1038/nature14864},
      url          = {https://pub.dzne.de/record/138158},
}