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000282938 1001_ $$aHeininger, Hannah$$b0
000282938 245__ $$aBACE1 regulates sleep–wake cycle through both enzymatic and non–enzymatic actions
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000282938 520__ $$aThe 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.
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000282938 7001_ $$0P:(DE-2719)9000546$$aFeng, Xiao$$b1$$udzne
000282938 7001_ $$aAltunkaya, Alp$$b2
000282938 7001_ $$00000-0002-5699-8063$$aZheng, Fang$$b3
000282938 7001_ $$00009-0002-9101-7491$$aStockinger, Florian$$b4
000282938 7001_ $$0P:(DE-2719)2810988$$aWefers, Benedikt$$b5$$udzne
000282938 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b6
000282938 7001_ $$0P:(DE-2719)9001718$$aGiesbertz, Pieter$$b7
000282938 7001_ $$0P:(DE-2719)9000794$$aTschirner, Sarah$$b8$$udzne
000282938 7001_ $$00009-0001-5047-4410$$aShqau, Dorina$$b9
000282938 7001_ $$aAdelsberger, Helmuth$$b10
000282938 7001_ $$aPonomarenko, Alexey$$b11
000282938 7001_ $$00000-0002-0132-9591$$aFenzl, Thomas$$b12
000282938 7001_ $$aAlzheimer, Christian$$b13
000282938 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b14$$eLast author
000282938 7001_ $$00000-0002-6414-8923$$aHuth, Tobias$$b15
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000282938 7870_ $$0DZNE-2025-01398$$aMüller, Stephan A et.al.$$dPRoteomics IDEntifications Database, 2025$$iRelatedTo$$r$$tDataset: Secretome and lysate proteomics of primary murine neurons with inactive BACE1
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