PXD058981 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-12-18 05:07:06 | ID requested | |
⏵ 1 | 2025-04-14 03:16:32 | announced | |
Publication List
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; |
Keyword List
submitter keyword: DIA, low input,TDP-43, ALS, FTD, timsTOF |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD058981
- Label: PRIDE project
- Name: Seeded aggregation of TDP-43 induces its loss of function