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PXD038399

PXD038399 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAlterations in SHH signal transduction introduce a state of hypometabolism in sporadic Parkinson's disease
DescriptionSporadic Parkinson’s Disease (sPD) is a progressive neurodegenerative disorder caused by a combination of genetic and environmental factors, however, the etiology remains largely elusive. Here, we used human iPSCs from late onset sPD patients, which were cultivated in vitro for up to 60 passages and screened for known PD associated alterations. Following long-term in vitro cultivation, exclusively neural cells derived from sPD patients developed a reduced mitochondrial respiration and glucose consumption reflecting a sPD specific state of hypometabolism. Integrated analysis of transcriptome, proteome and non-targeted metabolome data identified the citric acid cycle as being the bottleneck in sPD metabolism. A 13C metabolic flux analysis further unraveled the α-ketoglutarate dehydrogenase complex as being central for a reduced flux through the citric acid cycle. This resulted in a substrate availability problem for the electron transport chain and thus a reduced mitochondrial ATP production. Notably, this alterations in basal cellular metabolism were introduced by altered SHH signal transduction due to dysfunctional primary cilia. Upon inhibiting the enhanced SHH signal transduction in sPD, glucose uptake and the activity of the α-ketoglutarate dehydrogenase complex could be restored. Thus, inhibiting overactive SHH signaling maybe a potential neuroprotective therapy for sPD.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:05:01.732.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMario Oroshi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-11-26 04:11:46ID requested
12023-10-05 08:18:52announced
22024-10-22 06:05:02announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Mass Spectrometry, Neuronal Precursor cell,Parkinson's Disease, Proteomics
Contact List
Matthias Mann
contact affiliationMax Planck Institute of Biochemistry
contact emailmmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliationProteomics
contact emailoroshi@biochem.mpg.de
dataset submitter
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Dataset FTP location
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PRIDE project URI
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