PXD052897-1

PXD052897 is an original dataset announced via ProteomeXchange.

Title	Co-opting templated aggregation to selectively degrade pathogenic tau assemblies
Description	Protein aggregation causes a wide range of neurodegenerative diseases. Targeting and removing aggregates, but not the functional protein, is a considerable therapeutic challenge. Here we describe a therapeutic strategy called ‘RING-Bait’ which employs an aggregating protein sequence combined with an E3 ubiquitin ligase. RING-Bait is recruited into aggregates, whereupon clustering dimerises the RING domain and activates its E3 function, resulting in degradation of the aggregate complex. We exemplify this concept by demonstrating specific degradation of tau aggregates whilst sparing soluble tau. Unlike immunotherapy, RING-Bait is effective against both seeded and cell autonomous aggregation. RING-Bait removed tau aggregates seeded from AD and PSP brain extract and was also effective in primary neurons. We used brain penetrant AAV to treat P301S tau mice, reducing tau pathology and improving motor function. A RING-Bait strategy could be applied to other neurodegenerative proteinopathies by replacing the Bait sequence to match the target aggregate.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_18:56:01.660.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Catarina Franco
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-06 07:01:16	ID requested
⏵ 1	2025-05-06 18:56:02	announced

Miller LVC, Papa G, Vaysburd M, Cheng S, Sweeney PW, Smith A, Franco C, Katsinelos T, Huang M, Sanford SAI, Benn J, Farnsworth J, Higginson K, Joyner H, McEwan WA, James LC, Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function. Cell, 187(21):5967-5980.e17(2024) [pubmed]

10.1016/j.cell.2024.08.024;

submitter keyword: proteinopathies

Leo C. James
contact affiliation	MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
contact email	lcj@mrc-lmb.cam.ac.uk
lab head
Catarina Franco
contact affiliation	MRC Laboratory of Molecular Biology
contact email	cffranco@mrc-lmb.cam.ac.uk
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD052897

PRIDE project URI

• PRIDE
  1. PXD052897
     1. Label: PRIDE project
     2. Name: Co-opting templated aggregation to selectively degrade pathogenic tau assemblies