% 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”.

@MISC{Mller:279497,
      author       = {Müller, Stephan A and Lichtenthaler, Stefan},
      title        = {{D}ataset: {P}harmacoproteomics of non-human primate
                      cerebrospinal fluid after {BACE} inhibition},
      publisher    = {PRoteomics IDEntifications Database},
      reportid     = {DZNE-2025-00824},
      year         = {2023},
      abstract     = {The protease BACE1 is a major drug target for Alzheimer’s
                      disease, but chronic BACE1 inhibition is associated with
                      non-progressive worsening that may be caused by modulation
                      of unknown physiological BACE1 substrates. To identify in
                      vivo-relevant BACE1 substrates we applied pharmacoproteomics
                      to non-human-primate cerebrospinal fluid (CSF) after acute
                      treatment with BACE inhibitors. Besides SEZ6, the strongest,
                      dose-dependent reduction was observed for the
                      pro-inflammatory cytokine receptor gp130/IL6ST, which we
                      establish as a new in vivo BACE1 substrate. Gp130 was also
                      reduced in human CSF from a clinical trial with a BACE
                      inhibitor and in plasma of BACE1-deficient mice.
                      Mechanistically, we demonstrate that BACE1 directly cleaves
                      gp130, thereby attenuating membrane-bound gp130 and
                      increasing soluble gp130 abundance and controlling gp130
                      function in neuronal IL-6 signaling and neuronal survival
                      upon growth-factor withdrawal. In conclusion, BACE1 is a new
                      modulator of gp130 function. The BACE1-cleaved, soluble
                      gp130 may serve as a pharmacodynamic BACE1 activity marker
                      to reduce the occurrence of side effects of chronic BACE1
                      inhibition in humans.},
      cin          = {AG Lichtenthaler},
      cid          = {I:(DE-2719)1110006},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)32},
      url          = {https://pub.dzne.de/record/279497},
}