PXD066746

PXD066746 is an original dataset announced via ProteomeXchange.

Title	Polyserine-mediated targeting of FAF2/UBXD8 ameliorates tau aggregation
Description	Tau aggregation is a hallmark of several neurodegenerative disorders and gain of toxic functions of misfolded tau species are linked to pathobiology. Herein, we identified proteins that limit tau aggregation when targeted to tau aggregates by polyserine domains. Polyserine targeting was most effective at mitigating tau aggregation when fused to the VCP adaptor protein, FAF2/UBXD8. Surprisingly, FAF2/UBXD8 suppresses tau aggregation independent of VCP, but does require ubiquitination, membrane localization and a UBX domain. Validation in animal models demonstrated that polyserine-targeted FAF2/UBXD8 rescues tau-induced neurodegeneration in Drosophila. Further, delivery of targeted FAF2/UBXD8 reduced gliosis, seeding capacity and insoluble tau levels in PS19 tau transgenic mice while improving contextual fear conditioning. Collectively, our findings highlight polyserine as a tau targeting strategy and identify targeted FAF2/UBXD8 as a potent suppressor of tau pathology.
HostingRepository	PRIDE
AnnounceDate	2025-09-03
AnnouncementXML	Submission_2025-09-03_04:41:48.328.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD066746
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Meaghan Van Alstyne
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-29 23:30:31	ID requested
⏵ 1	2025-09-03 04:41:48	announced

10.1016/J.NEURON.2025.08.002;

10.6019/PXD066746;

submitter keyword: TMT-pro

Roy Parker
contact affiliation	University of Colorado Boulder; Howard Hughes Medical Institute
contact email	roy.parker@colorado.edu
lab head
Meaghan Van Alstyne
contact affiliation	University of Colorado Boulder
contact email	meva1786@colorado.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066746
     1. Label: PRIDE project
     2. Name: Polyserine-mediated targeting of FAF2/UBXD8 ameliorates tau aggregation