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PXD075048

PXD075048 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomics of iPSC derived ENLs from Parkinson's Disease patients
DescriptionGastrointestinal (GI) dysfunction precedes motor symptoms in Parkinson disease (PD), implicating the enteric nervous system (ENS) in early disease pathogenesis. However, how the PD-associated protein alpha synuclein (alpha syn) contributes to ENS dysfunction, and whether this is influenced by inflammation, remains unresolved. Here, we show that tumor necrosis factor alpha (TNF alpha) increases alpha syn accumulation at mitochondria, disrupts the malate-aspartate shuttle (MAS), and induces a metabolic shift toward glutamine oxidation in iPSC derived enteric neural lineages (ENLs) from PD patients carrying alpha syn gene triplications. This metabolic rewiring leads to mitochondrial dysfunction, NAD+ depletion, and oxidative stress. Targeting glutamate metabolism with Chicago Sky Blue 6B restores mitochondrial function and reverses TNF alpha induced metabolic impairment. Combined transcriptomic and histological analyses of human gut tissue show that inflammation-associated MAS suppression and alpha syn upregulation are not confined to PD but are general hallmarks of intestinal inflammation. These findings highlight a conserved metabolic vulnerability in the ENS and establish iPSC ENLs as a powerful platform for modeling early inflammatory disease mechanisms.
HostingRepositoryMassIVE
AnnounceDate2026-02-28
AnnouncementXMLSubmission_2026-02-28_08:21:02.737.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBruno
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-02-28 08:08:55ID requested
12026-02-28 08:21:03announced
Publication List
no publication
Keyword List
submitter keyword: iPSC, Parkinson, enteric, DatasetType:Proteomics
Contact List
Beate Winner
contact affiliationFriedrich Alexander Universitat Erlangen Nurnberg
contact emailbeate.winner@fau.de
lab head
Bruno
contact affiliationFriedrich-Alexander Universitat Erlangen-Nurnberg
contact emailbrghirotto@gmail.com
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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