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Secretome and lysate proteomics of primary murine neurons with inactive BACE1

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 analyzed sleep patterns in both BACE1-KO mice and a newly generated transgenic line expressing a proteolysis-deficient BACE1 variant (BACE1-KI). To investigate changes in the cellular proteome as well as the secretome, primary neurons were metabolically labeled with ManNAz and the secretome was anlyzed using the hiSPECS method. The results showed areduction of several BACE1 substrates in the secretome (i.e. SEZ6, APLP1) as well as an accumulation of some BACE1 substrates in the lysate (i.e. APLP1, SEZ6, CNTN2).

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebral Cortex Neuron

SUBMITTER: Stephan Mueller

LAB HEAD: Dr Stefan F. Lichtenthaler

PROVIDER: PXD065011 | Pride | 2025-12-10

REPOSITORIES: Pride

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			Action	DRS
	197-1-1_Slot2-4_1_5835.d.zip	Other
	197-1-2_Slot2-12_1_5843.d.zip	Other
	197-2-1_Slot2-30_1_5861.d.zip	Other
	197-2-2_Slot2-38_1_5869.d.zip	Other
	197-3-1_Slot2-15_1_5846.d.zip	Other

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