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| 001 | 279497 | ||
| 005 | 20250709100939.0 | ||
| 037 | _ | _ | |a DZNE-2025-00824 |
| 100 | 1 | _ | |a Müller, Stephan A |0 P:(DE-2719)2810938 |b 0 |u dzne |
| 245 | _ | _ | |a Dataset: Pharmacoproteomics of non-human primate cerebrospinal fluid after BACE inhibition |
| 260 | _ | _ | |c 2023 |b PRoteomics IDEntifications Database |
| 336 | 7 | _ | |a MISC |2 BibTeX |
| 336 | 7 | _ | |a Dataset |b dataset |m dataset |0 PUB:(DE-HGF)32 |s 1752047420_8072 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a Chart or Table |0 26 |2 EndNote |
| 336 | 7 | _ | |a Dataset |2 DataCite |
| 336 | 7 | _ | |a DATA_SET |2 ORCID |
| 336 | 7 | _ | |a ResearchData |2 DINI |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 352 - Disease Mechanisms (POF4-352) |0 G:(DE-HGF)POF4-352 |c POF4-352 |f POF IV |x 0 |
| 700 | 1 | _ | |a Lichtenthaler, Stefan |0 P:(DE-2719)2181459 |b 1 |u dzne |
| 787 | 0 | _ | |a Müller, Stephan A. et.al. |d London : Biomed Central, 2023 |i RelatedTo |0 DZNE-2023-00286 |r |t The Alzheimer’s disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130 |
| 856 | 4 | _ | |u https://wwwdev.ebi.ac.uk/pride/archive/projects/PXD035141 |
| 909 | C | O | |o oai:pub.dzne.de:279497 |p VDB |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 0 |6 P:(DE-2719)2810938 |
| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 1 |6 P:(DE-2719)2181459 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Neurodegenerative Diseases |1 G:(DE-HGF)POF4-350 |0 G:(DE-HGF)POF4-352 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Disease Mechanisms |x 0 |
| 920 | 1 | _ | |0 I:(DE-2719)1110006 |k AG Lichtenthaler |l Neuroproteomics |x 0 |
| 980 | _ | _ | |a dataset |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-2719)1110006 |
| 980 | _ | _ | |a UNRESTRICTED |
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