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PXD058981

PXD058981 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSeeded aggregation of TDP-43 induces its loss of function
DescriptionNeurodegeneration 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.
HostingRepositoryPRIDE
AnnounceDate2025-04-14
AnnouncementXMLSubmission_2025-04-14_03:16:31.831.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterWeijia Zhong
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro 2
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-12-18 05:07:06ID requested
12025-04-14 03:16:32announced
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 affiliationUniversity of Zurich Department of Quantitative Biomedicine
contact emailmagdalini.polymenidou@uzh.ch
lab head
Weijia Zhong
contact affiliationUniversity of Zurich Department of Quantitative Biomedicine Polymenidou Lab
contact emailweijia.zhong@uzh.ch
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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