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PXD037299-1

PXD037299 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss
DescriptionThe dynamic function of synapses is critical for encoding memories in the brain. Pathogenic tau obstructs glutamatergic synapse function by blocking long-term potentiation (LTP), representing a key mechanism underlying memory impairment in Alzheimer s disease (AD). Here we developed a strategy for KIdney/BRAin (KIBRA)-mediated LTP repair in neurons with pathogenic tau using the C-terminus of KIBRA (CT-KIBRA). We show that CT-KIBRA restores LTP and memory in transgenic mice expressing human tau that mimics pathogenic hyperacetylated tau found in AD and other tauopathies. CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss in the transgenic mouse brain, instead, we show that CT-KIBRA binds to and stabilizes protein kinase M zeta (PKM zeta) to maintain plasticity and memory despite tau pathogenesis. Further, in humans we established that KIBRA levels in brain and cerebrospinal fluid correlate with tau and cognitive impairment in tauopathies. Our study provides evidence to support KIBRA as a tauopathy-related synaptic biomarker and a synapse repair therapeutic to ameliorate cognitive impairment.
HostingRepositoryMassIVE
AnnounceDate2023-10-31
AnnouncementXMLSubmission_2023-10-31_15:46:44.895.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJoanna Bons
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentTripleTOF 6600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-10-11 11:29:23ID requested
12023-10-31 15:46:45announced
Publication List
no publication
Keyword List
submitter keyword: KIBRA, Alzheimer's disease, Synapses, Data-independent acquisition (DIA), Quantitative proteomics
Contact List
Birgit Schilling
contact affiliationBuck Institute
contact emailbschilling@buckinstitute.org
lab head
Joanna Bons
contact affiliationBuck Institute for Research on Aging
contact emailjbons@buckinstitute.org
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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