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PXD060223-1

PXD060223 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA role for the autophagy receptor NBR1 in the degradation of Tau aggregates
DescriptionNeurofibrillary tangles (NFTs), comprising hyperphosphorylated and aggregated Tau protein, are a primary neuropathological feature of Alzheimer's Disease (AD). In patients, the formation and spread of NFTs across the brain correlate with cognitive decline. However, the mechanisms driving Tau aggregation and leading to the subsequent neuronal dysfunction are not fully understood. In this study, we explored proteomic and phosphoproteomic changes resulting from the seed-induced aggregation of endogenous Tau in human neurons derived from induced pluripotent stem (iPS) cells. We discovered previously undescribed phosphorylation sites on NBR1, an autophagy receptor, which were significantly altered by Tau aggregation in vitro. We further show that NBR1 directly interacts with phosphorylated Tau and Tau aggregates in various cell models. This interaction is associated with autophagic Tau degradation in HEK cells, and siRNA-mediated knockdown of NBR1 significantly increases Tau aggregate levels in iPS-derived neurons. Additionally, we find that NBR1 specifically interacts with phospho-Tau in human AD brain, underscoring the relevance of our findings to the human disease. These insights provide a deeper understanding of the molecular interactions between autophagy receptors and Tau pathology in AD and reveal a role for NBR1 as an important receptor for pathological forms of Tau.
HostingRepositoryMassIVE
AnnounceDate2025-08-15
AnnouncementXMLSubmission_2025-08-15_09:25:36.982.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMarie Neu
SpeciesList scientific name: human;
ModificationListPhospho
InstrumentOrbitrap Exploris 240
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-01-27 00:38:43ID requested
12025-08-15 09:25:37announced
Publication List
no publication
Keyword List
submitter keyword: Alzheimer's Disease, Tau aggregation, phospho-proteomics, proteomics, autophagy receptor, Tau, iPS-derived neurons, mass spectrometry, DatasetType:Proteomics
Contact List
Marie Neu
contact affiliationAbbvie Deutschland GmbH & Co-KG
contact emailmarie.neu@abbvie.com
lab head
Marie Neu
contact affiliationAbbvie Deutschland Gmbh& Co KG
contact emailmarie.neu@abbvie.com
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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