PXD000866 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic/lysosomal dysfunction and impaired calcium homeostasis |
Description | Mutations in the acid β-glucocerebrosidase (GBA1) gene, responsible for the lysosomal storage disorder Gaucher’s disease (GD), are the strongest genetic risk factor for Parkinson’s disease (PD) known to date. To elucidate the mechanisms underlying neurodegeneration in these patients, we generated induced pluripotent stem cells from subjects with GD and PD harboring GBA1 mutations and differentiated them to midbrain dopaminergic neurons. Highly enriched neurons showed a reduction of glucocerebrosidase activity and protein levels, increased glucosylceramide and α-synuclein levels and autophagic/lysosomal defects. Quantitative proteomics profiling revealed an increase of the neuronal calcium-binding protein 2 (NECAB2) in diseased neurons. We found dysregulation of calcium homeostasis and increased vulnerability to stress responses involving elevation of cytosolic calcium in mutant neurons. Importantly, correction of the mutations rescued such pathological phenotypes. Our findings provide evidence for a link between GBA1 mutations and complex changes in autophagic/lysosomal system and intracellular calcium homeostasis, which underlie vulnerability to neurodegeneration. |
HostingRepository | PRIDE |
AnnounceDate | 2014-06-03 |
AnnouncementXML | Submission_2014-06-03_03:58:34.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Fiona McAllister |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2014-04-01 05:27:02 | ID requested | |
⏵ 1 | 2014-06-03 03:58:35 | announced | |
2 | 2014-06-16 01:25:06 | announced | Updated publication reference for PubMed record(s): 24905578. |
3 | 2014-07-24 05:17:07 | announced | Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Neurons, human, TMT |
Contact List
Michela Deleidi |
contact affiliation | Dept. for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Tubingen, Germany |
contact email | michela.deleidi@dzne.de |
lab head | |
Fiona McAllister |
contact affiliation | Stanford |
contact email | fionaemca@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD000866
- Label: PRIDE project
- Name: iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic/lysosomal dysfunction and impaired calcium homeostasis