PXD038399 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Alterations in SHH signal transduction introduce a state of hypometabolism in sporadic Parkinson's disease |
Description | Sporadic 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:05:01.732.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mario Oroshi |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-11-26 04:11:46 | ID requested | |
1 | 2023-10-05 08:18:52 | announced | |
⏵ 2 | 2024-10-22 06:05:02 | announced | 2024-10-22: 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 affiliation | Max Planck Institute of Biochemistry |
contact email | mmann@biochem.mpg.de |
lab head | |
Mario Oroshi |
contact affiliation | Proteomics |
contact email | oroshi@biochem.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD038399
- Label: PRIDE project
- Name: Alterations in SHH signal transduction introduce a state of hypometabolism in sporadic Parkinson's disease