% 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{Dunot:271713,
      author       = {Dunot, Jade and Moreno, Sebastien and Gandin, Carine and
                      Pousinha, Paula A and Amici, Mascia and Dupuis, Julien and
                      Anisimova, Margarita and Winschel, Alex and Uriot, Magalie
                      and Petshow, Samuel J and Mensch, Maria and Bethus, Ingrid
                      and Giudici, Camilla and Hampel, Heike and Wefers, Benedikt
                      and Wurst, Wolfgang and Naumann, Ronald and Ashby, Michael C
                      and Laube, Bodo and Zito, Karen and Mellor, Jack R and Groc,
                      Laurent and Willem, Michael and Marie, Hélène},
      title        = {{APP} fragment controls both ionotropic and non-ionotropic
                      signaling of {NMDA} receptors.},
      journal      = {Neuron},
      volume       = {112},
      number       = {16},
      issn         = {0896-6273},
      address      = {New York, NY},
      publisher    = {Elsevier},
      reportid     = {DZNE-2024-01065},
      pages        = {2708 - 2720.e9},
      year         = {2024},
      abstract     = {NMDA receptors (NMDARs) are ionotropic receptors crucial
                      for brain information processing. Yet, evidence also
                      supports an ion-flux-independent signaling mode mediating
                      synaptic long-term depression (LTD) and spine shrinkage.
                      Here, we identify AETA (Aη), an amyloid-β precursor
                      protein (APP) cleavage product, as an NMDAR modulator with
                      the unique dual regulatory capacity to impact both signaling
                      modes. AETA inhibits ionotropic NMDAR activity by competing
                      with the co-agonist and induces an intracellular
                      conformational modification of GluN1 subunits. This favors
                      non-ionotropic NMDAR signaling leading to enhanced LTD and
                      favors spine shrinkage. Endogenously, AETA production is
                      increased by in vivo chemogenetically induced neuronal
                      activity. Genetic deletion of AETA production alters NMDAR
                      transmission and prevents LTD, phenotypes rescued by acute
                      exogenous AETA application. This genetic deletion also
                      impairs contextual fear memory. Our findings demonstrate
                      AETA-dependent NMDAR activation (ADNA), characterizing AETA
                      as a unique type of endogenous NMDAR modulator that exerts
                      bidirectional control over NMDAR signaling and associated
                      information processing.},
      keywords     = {Humans / Receptors, N-Methyl-D-Aspartate: metabolism /
                      Animals / Mice / Amyloid beta-Protein Precursor: genetics /
                      Amyloid beta-Protein Precursor: metabolism / Signal
                      Transduction: physiology / Long-Term Synaptic Depression:
                      physiology / Long-Term Synaptic Depression: drug effects /
                      Mice, Inbred C57BL / Mice, Knockout / Fear: physiology /
                      Hippocampus: metabolism / Neurons: metabolism / Dendritic
                      Spines: metabolism / Memory: physiology / Rats / APP (Other)
                      / NMDA receptors (Other) / amyloid-β precursor protein
                      (Other) / eta-secretase (Other) / hippocampus (Other) /
                      long-term depression (Other) / memory (Other) /
                      non-ionotropic signaling (Other) / spine shrinkage (Other) /
                      synapse (Other) / Receptors, N-Methyl-D-Aspartate (NLM
                      Chemicals) / Amyloid beta-Protein Precursor (NLM Chemicals)},
      cin          = {AG Haass / AG Wurst},
      ddc          = {610},
      cid          = {I:(DE-2719)1110007 / I:(DE-2719)1140001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38878768},
      pmc          = {pmc:PMC11343662},
      doi          = {10.1016/j.neuron.2024.05.027},
      url          = {https://pub.dzne.de/record/271713},
}