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@ARTICLE{Oberlnder:282582,
      author       = {Oberländer, Kristin and Pruunsild, Priit and Koch, Philipp
                      and Yan, Jing and Szafranski, Karol and Bading, Hilmar},
      title        = {{I}nhba, {H}omer1 and {B}dnf are major targets of
                      transcriptomic dysregulation by neurodegenerative
                      disease-associated excitotoxic {NMDA} receptor signaling.},
      journal      = {Communications biology},
      volume       = {8},
      number       = {1},
      issn         = {2399-3642},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DZNE-2025-01342},
      pages        = {1743},
      year         = {2025},
      abstract     = {Synaptic activity-regulated gene expression supports
                      neuroprotection, plasticity, and memory. The transcription
                      factor CREB is central to these processes. It is activated
                      by synaptic NMDA receptors but inactivated by excitotoxic
                      extrasynaptic NMDAR (esNMDAR) signaling. Using primary
                      hippocampal neurons, we modeled neurodegeneration and found
                      that esNMDAR activation, which causes CREB shut-off and
                      inactivation of the ERK/MAPK-ELK1/SRF pathway, extensively
                      distorted control of synaptic activity over transcription.
                      This resulted in the suppression of key neuroprotective
                      genes, in particular Inhba and Bdnf, but also of genes
                      involved in synaptic function (Homer1, Btg2, Mir132, Mir212)
                      and transcription factor genes (Atf3, Egr1, Fos, Npas4). In
                      a Huntington's disease (HD) mouse model, treatment with
                      memantine or targeting the NMDAR/TRPM4 complex with FP802
                      restored gene expression, notably Inhba, Homer1 and Bdnf,
                      and attenuated the decrease of the HD disease marker Ppp1r1b
                      (DARPP-32). These findings identify esNMDAR-driven
                      transcriptional dysregulation as a key pathomechanism in
                      neurodegenerative disease, supporting inhibition of
                      esNMDAR-signaling as a promising therapeutic approach.},
      keywords     = {Animals / Brain-Derived Neurotrophic Factor: genetics /
                      Brain-Derived Neurotrophic Factor: metabolism / Receptors,
                      N-Methyl-D-Aspartate: metabolism / Receptors,
                      N-Methyl-D-Aspartate: genetics / Homer Scaffolding Proteins:
                      genetics / Homer Scaffolding Proteins: metabolism / Mice /
                      Signal Transduction / Transcriptome / Neurodegenerative
                      Diseases: metabolism / Neurodegenerative Diseases: genetics
                      / Hippocampus: metabolism / Neurons: metabolism / Huntington
                      Disease: genetics / Huntington Disease: metabolism / Gene
                      Expression Regulation / Disease Models, Animal / Male /
                      Mice, Inbred C57BL / Brain-Derived Neurotrophic Factor (NLM
                      Chemicals) / Receptors, N-Methyl-D-Aspartate (NLM Chemicals)
                      / Homer Scaffolding Proteins (NLM Chemicals) / Homer1
                      protein, mouse (NLM Chemicals) / Bdnf protein, mouse (NLM
                      Chemicals)},
      cin          = {AG Schneider},
      ddc          = {570},
      cid          = {I:(DE-2719)1011305},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41339520},
      doi          = {10.1038/s42003-025-09074-9},
      url          = {https://pub.dzne.de/record/282582},
}