PXD063433

PXD063433 is an original dataset announced via ProteomeXchange.

Title	Vimentin network dysregulation mediates neurite deficits in SNCA duplication Parkinson’s patient-derived midbrain neurons
Description	Duplication of the SNCA gene (SNCADupl), linked to elevated levels of alpha-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from PD SNCADupl patients identified neuritic deficits, accompanied by decreased levels of cytoskeletal element b-tubulin-III (bTubIII). To explore mechanisms underlying these effects in SNCADupl neurons, we employed CRISPR/Cas9 to generate isogenic control hiPSCs. Isogenic correction of SNCA dosage restored SNCADupl-induced neurite defects and bTubIII levels. Multi-omics analyses revealed SNCADupl-induced alterations in neuronal differentiation, with a notable downregulation of PAX6. Moreover, SNCADupl induced an upregulation of vimentin. Further characterization revealed heightened vimentin truncation, associated with altered distribution and organization. Similar changes in vimentin levels and truncation were observed in post-mortem putamen tissue from sporadic PD patients. Notably, targeting vimentin with okadaic acid and withaferin A restored bTubIII- and neurite-associated defects, suggesting its potential to prevent aSyn-mediated neuritic degeneration.
HostingRepository	PRIDE
AnnounceDate	2025-07-16
AnnouncementXML	Submission_2025-07-16_13:52:02.675.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Kielkowski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-29 02:07:26	ID requested
⏵ 1	2025-07-16 13:52:03	announced

Dataset with its publication pending

submitter keyword: SNCA, midbrain neurons,Parkinsons disease, vimentin

Wei Xiang
contact affiliation	Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg,91054 Erlangen, Germany.
contact email	wei.xiang@uk-erlangen.de
lab head
Pavel Kielkowski
contact affiliation	LMU Munich
contact email	pavel.kielkowski@cup.lmu.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/2025/07/PXD063433

PRIDE project URI

• PRIDE
  1. PXD063433
     1. Label: PRIDE project
     2. Name: Vimentin network dysregulation mediates neurite deficits in SNCA duplication Parkinson’s patient-derived midbrain neurons