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@ARTICLE{Heininger:282938,
      author       = {Heininger, Hannah and Feng, Xiao and Altunkaya, Alp and
                      Zheng, Fang and Stockinger, Florian and Wefers, Benedikt and
                      Müller, Stephan A and Giesbertz, Pieter and Tschirner,
                      Sarah and Shqau, Dorina and Adelsberger, Helmuth and
                      Ponomarenko, Alexey and Fenzl, Thomas and Alzheimer,
                      Christian and Lichtenthaler, Stefan F and Huth, Tobias},
      title        = {{BACE}1 regulates sleep–wake cycle through both enzymatic
                      and non–enzymatic actions},
      journal      = {EMBO reports},
      volume       = {Advance online publication},
      issn         = {1469-221X},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DZNE-2025-01399},
      pages        = {-},
      year         = {2025},
      abstract     = {The β-secretase BACE1 has become a prime target in
                      Alzheimer’s disease (AD) therapy, because it drives the
                      production of pathogenic amyloid β peptides. However,
                      clinical trials with BACE1-targeting drugs were halted due
                      to adverse effects on cognitive performance. We propose here
                      that cognitive impairment by BACE1 inhibitors may be a
                      corollary of a higher function of BACE1 related to proper
                      sleep regulation. To address non-enzymatic effects of BACE1
                      on ion channels likely involved in the sleep-wake cycle, we
                      analyze sleep patterns in both BACE1-KO mice and a newly
                      generated transgenic line expressing a proteolysis-deficient
                      BACE1 variant (BACE1-KI). We find that BACE1-KI and BACE1-KO
                      mice display common and distinct sleep-wake disturbances.
                      Compared with their respective wild-type littermates, both
                      mutant lines sleep less during the light phase (when they
                      preferentially rest). Furthermore, transition rates between
                      wake and sleep states are altered, as are sleep spindles and
                      EEG power spectra mainly in the gamma range. Thus, a better
                      understanding of how BACE1 interferes with sleep-modulated
                      behaviors is needed if clinical trials with BACE1-targeted
                      inhibitors are to resume.},
      cin          = {AG Lichtenthaler / AG Wurst},
      ddc          = {570},
      cid          = {I:(DE-2719)1110006 / I:(DE-2719)1140001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1038/s44319-025-00604-4},
      url          = {https://pub.dzne.de/record/282938},
}