PXD058981

PXD058981 is an original dataset announced via ProteomeXchange.

Title	Seeded aggregation of TDP-43 induces its loss of function
Description	Neurodegeneration in ALS and FTD results from both gain of toxicity and loss of normal function of the RNA-binding protein TDP-43, but their mechanistic connection remains unclear. Increasing evidence suggests that TDP-43 aggregates act as self-templating seeds, propagating pathology through the central nervous system via a prion-like cascade. We developed a robust TDP-43 seeding platform for quantitative, high-throughput assessment of TDP-43 aggregate uptake, cell-to-cell spreading and loss of function within living cells, while they progress towards pathology. We show that both patient-derived and recombinant TDP-43 pathological aggregates were abundantly internalized in human neuron-like cells, efficiently recruited endogenous TDP-43 and formed cytoplasmic inclusions reminiscent of ALS/FTD pathology. These neoaggregates progressively drove the nuclear egress of TDP-43 leading to its loss of function. Our model demonstrates the link between TDP-43 aggregation and aberrant cryptic splicing and provides new tools to identify genetic or pharmacologic modifiers of each step in the process.
HostingRepository	PRIDE
AnnounceDate	2025-04-14
AnnouncementXML	Submission_2025-04-14_03:16:31.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weijia Zhong
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-18 05:07:06	ID requested
⏵ 1	2025-04-14 03:16:32	announced

Scial, ò C, Zhong W, Jagannath S, Wilkins O, Caredio D, Hruska-Plochan M, Lurati F, Peter M, De Cecco E, Celauro L, Aguzzi A, Legname G, Fratta P, Polymenidou M, Seeded aggregation of TDP-43 induces its loss of function and reveals early pathological signatures. Neuron, 113(10):1614-1628.e11(2025) [pubmed]

10.1016/j.neuron.2025.03.008;

submitter keyword: DIA, low input,TDP-43, ALS, FTD, timsTOF

Magdalini Polymenidou
contact affiliation	University of Zurich Department of Quantitative Biomedicine
contact email	magdalini.polymenidou@uzh.ch
lab head
Weijia Zhong
contact affiliation	University of Zurich Department of Quantitative Biomedicine Polymenidou Lab
contact email	weijia.zhong@uzh.ch
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/2025/04/PXD058981

PRIDE project URI

• PRIDE
  1. PXD058981
     1. Label: PRIDE project
     2. Name: Seeded aggregation of TDP-43 induces its loss of function