PXD053387

PXD053387 is an original dataset announced via ProteomeXchange.

Title	Axonal tau reduction ameliorates tau and amyloid pathology in a mouse model of Alzheimer’s disease
Description	Pathological deposition of hyperphosphorylated tau in the brain closely correlates with the course of Alzheimer´s disease (AD). Tau pathology occurs first in axons of affected neurons and tau removal from axons might thus be an early intervention strategy. We report that the RNA-binding protein hnRNP R facilitates the axonal localization of the Mapt mRNA encoding tau. Mapt mRNA and tau protein were reduced in axons but not cell bodies of primary neurons cultured from hnRNP R knockout mice. Brains of 5xFAD mice deficient for hnRNP R contained less phospho-tau aggregates and amyloid-β plaques in cortex and hippocampus. Treatment of neurons with antisense oligonucleotides (MAPT-ASOs) to block hnRNP R binding to Mapt similarly reduced axonal tau levels, and intracerebroventricular injection of a MAPT-ASO ameliorated the phospho-tau and plaque load in 5xFAD mice. Lowering of tau selectively in axons thus represents an innovative therapeutic perspective for treatment of AD and other tauopathies.
HostingRepository	PRIDE
AnnounceDate	2025-08-04
AnnouncementXML	Submission_2025-08-03_17:10:09.897.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-25 01:00:12	ID requested
⏵ 1	2025-08-03 17:10:10	announced

10.1186/s40035-025-00499-0;

Zare A, Salehi S, Bader JM, Wiessler AL, Prokesch M, Albrecht V, Villmann C, Mann M, Briese M, Sendtner M, Axonal tau reduction ameliorates tau and amyloid pathology in a mouse model of Alzheimer's disease. Transl Neurodegener, 14(1):39(2025) [pubmed]

submitter keyword: antisense oligonucleotide,Alzheimer´s disease, amyloid, tau, hnRNP R

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
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/2025/08/PXD053387

PRIDE project URI

• PRIDE
  1. PXD053387
     1. Label: PRIDE project
     2. Name: Axonal tau reduction ameliorates tau and amyloid pathology in a mouse model of Alzheimer’s disease