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PXD068396-1

PXD068396 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePrPC-facilitated cell-signaling activates phospholipase Cgamma1 and triggers an Arc/Arg3.1 response in mouse neurons and human iPSC-derived neurons
DescriptionSynapse loss is an early feature of prion disease, yet the underlying drivers are poorly understood. We recently revealed evidence of neuronal hyperactivity in prion-infected animal models. Herein we identified increased Arc/Arg3.1 in patients with prion disease, suggesting heightened neuronal activity also occurs in human prion-affected brain. To determine the signaling events initiated by prion aggregates (PrPSc), we developed a disease model in which human iPSC-derived excitatory neurons (iNs) are stimulated with a PrPSc-mimetic antibody that binds the cellular prion protein. Within two hours, we detected an Arc response together with transcriptomic changes previously reported in prion-infected mice. Proteomics, RNA sequencing, and a phosphokinase array revealed altered phosphorylation changes of PLC-gamma1, ERK1/2, and EGFR as PrPC-triggered cell signaling events accompanying the Arc/Arg3.1 response. These results suggest that PrPC ligands, including PrPSc, may trigger rapid signaling events linked to neuronal hyperactivity in human neurons, and indicate PLC-gamma1 as a potential interventional target.
HostingRepositoryMassIVE
AnnounceDate2026-04-01
AnnouncementXMLSubmission_2026-04-01_16:42:12.849.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDaniel McClatchy
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-09-15 17:06:30ID requested
12026-04-01 16:42:13announced
Publication List
no publication
Keyword List
submitter keyword: Prion Disease, Neurodegeneration, Proteomics, Alzheimer's disease, protein misfolding, DatasetType:Proteomics
Contact List
Christina Sigurdson
contact affiliationUC San Diego
contact emailcsigurdson@health.ucsd.edu
lab head
Daniel McClatchy
contact affiliationTSRI
contact emaildmcclat@scripps.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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