⮝ Full datasets listing
PXD064860-1
PXD064860 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Oxidative stress decreases deubiquitylases and proteasome activity during vertebrate brain aging |
| Description | The ubiquitin-proteasome system (UPS) is essential for maintaining neuronal proteostasis. However, how deubiquitylating enzymes (DUBs), key regulators of substrate stability and signaling, functionally change during brain aging in vertebrates remains poorly understood. We systematically profiled active cysteine DUBs using activity based proteomics in aging mouse 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 longitudinal 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-03-04 |
| AnnouncementXML | Submission_2026-03-04_04:26:23.997.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Leibniz FLI Proteomics |
| SpeciesList | scientific name: Nothobranchius furzeri; common name: turquoise killifish; NCBI TaxID: 105023; |
| ModificationList | Biotin; Oxidation; Carbamidomethyl |
| Instrument | Orbitrap Exploris 480 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-06-11 00:34:26 | ID requested | |
| ⏵ 1 | 2026-03-04 04:26:24 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Brain aging, Deubiquitylases (DUBs), Activity based proteomics, Oxidative stress, Ubiquitin proteasome system (UPS), NACET, DatasetType:Proteomics |
Contact List
| Alessandro Ori | |
|---|---|
| contact affiliation | Leibniz Institute on Aging Fritz Lipmann Institute (FLI) |
| contact email | alessandro.ori@leibniz-fli.de |
| lab head | |
| Leibniz FLI Proteomics | |
| contact affiliation | Leibniz FLI |
| contact email | proteomics@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/v10/MSV000098114/ |
