PXD065011-1

PXD065011 is an original dataset announced via ProteomeXchange.

Title	Secretome and lysate proteomics of primary murine neurons with inactive BACE1
Description	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).
HostingRepository	PRIDE
AnnounceDate	2025-12-11
AnnouncementXML	Submission_2025-12-10_16:56:37.754.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephan Mueller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-13 12:55:25	ID requested
⏵ 1	2025-12-10 16:56:38	announced

10.1038/S44319-025-00604-4;

submitter keyword: neurons,Mouse, hiSPECS, BACE1, secretome

Dr Stefan F. Lichtenthaler
contact affiliation	DZNE Munich, Neuroproteomics, Feodor-Lynen-Str. 17, 81377 München, Germany
contact email	stefan.lichtenthaler@dzne.de
lab head
Stephan Mueller
contact affiliation	DZNE Munich Neuroproteomics
contact email	stephan.mueller@dzne.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065011
     1. Label: PRIDE project
     2. Name: Secretome and lysate proteomics of primary murine neurons with inactive BACE1