⮝ Full datasets listing

PXD072807

PXD072807 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains - DUB
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. We identified a subset of DUBs that progressively lose catalytic activity with age, despite stable protein levels. We demonstrated that oxidative stress impairs DUB function through thiol oxidation and that antioxidant treatment by N-acetylcysteine ethyl ester (NACET) restores their activity in vitro and in vivo. Moreover, global DUB inhibition as well as targeted inhibition of USP7, one of the DUBs most strongly affected during aging, in human iPSC-derived neurons partially recapitulated ubiquitylation changes observed in aged brains. Temporal analysis in mice further 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_04:27:21.566.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;
ModificationListAcetyl; Biotin; Oxidation; Carbamidomethyl
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-01-08 02:08:37ID requested
12026-03-04 04:27:22announced
Publication List
no publication
Keyword List
submitter keyword: Brain aging, Deubiquitylases (DUBs), Activity-based proteomics, Oxidative stress, Ubiquitin-Proteasome System (UPS), USP7, 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
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v11/MSV000100403/