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PXD067249-1

PXD067249 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOxidative stress decreases deubiquitylases and proteasome activity during vertebrate brain aging - PRM Analysis
DescriptionThe ubiquitin-proteasome system is essential for neuronal proteostasis and its activity declines with age. How deubiquitylating enzymes (DUBs) are affected by aging in the vertebrate brain remains unclear. Here, we profiled cysteine protease DUBs using activity-based proteomics in aging mice and killifish brains. Despite stable protein levels, we identified a subset of DUBs that progressively lose catalytic activity with age. We demonstrated that oxidative stress impairs DUB function through thiol oxidation and that antioxidant treatment restores their activity in vitro and in vivo. Further, inhibition of DUBs in human iPSC-derived neurons significantly recapitulated ubiquitylation changes observed in aged brains, and temporal analysis in mice revealed that DUB inhibition precedes proteasome decline in the brain during aging. Together, these findings indicate a redox-sensitive subset of DUBs that undergo an age-associated decline in activity and suggest that impaired deubiquitylation is an early, yet potentially reversible, driver of proteostasis decline in the aging brain.
HostingRepositoryMassIVE
AnnounceDate2026-03-04
AnnouncementXMLSubmission_2026-03-04_04:29:25.617.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLeibniz FLI Proteomics
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListOxidation; Carbamidomethyl; GG
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-08-12 00:22:57ID requested
12026-03-04 04:29:26announced
Publication List
no publication
Keyword List
submitter keyword: Brain aging, Deubiquitylases (DUBs), Activity-based proteomics, Oxidative stress, Ubiquitin-proteasome system (UPS), N-acetylcysteine ethyl ester (NACET, DatasetType:Proteomics
Contact List
Alessandro Ori
contact affiliationLeibniz Institute on Aging Fritz Lipmann Institute (FLI)
contact emailalessandro.ori@leibniz-fli.de
lab head
Leibniz FLI Proteomics
contact affiliationLeibniz FLI
contact emailproteomics@leibniz-fli.de
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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