PXD057491 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Proteostasis dysregulation in p.A53T--Synuclein iPSC-derived astrocytes exacerbates neurodegeneration in a Parkinson’s disease model with Lewy-like pathology |
| Description | Alpha-Synuclein (Syn) plays a central role in Parkinson’s disease (PD) and the p.A53T mutation causes an early-onset familial form of PD with severe manifestations. The pathological effects of the p.A53T-Syn mutation have been extensively investigated in neurons, yet the consequences on astrocytes and astrocytic contribution to PD pathology are understudied. Here, we differentiated induced pluripotent stem cells from PD patients carrying the p.A53T-Syn mutation to astrocytes, which uncovered cell-intrinsic phenotypes, including calcium dyshomeostasis and accumulation of protein aggregates. Proteomic profiling and functional analyses revealed perturbed protein catabolic processes, involving the proteasome and autophagy, associated with lysosomal malfunction. Dopamine neurons co-cultured with p.A53T-Syn astrocytes displayed exacerbated neurodegeneration with hallmark Lewy-like pathologies, rescued by control astrocytes due to their ability to resolve neuronal Syn aggregates by endocytic clearance. Our findings underscore a critical impact of p.A53T-Syn on astrocytic protein quality control mechanisms, positioning astrocytes as important contributors to PD neuropathology. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-10-27 |
| AnnouncementXML | Submission_2025-10-27_07:19:08.444.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Martina Samiotaki |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
| Instrument | Q Exactive HF-X |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2024-11-04 09:12:11 | ID requested | |
| ⏵ 1 | 2025-10-27 07:19:08 | announced | |
Publication List
Keyword List
| submitter keyword: ubiquitin-proteasome system, autophagy-lysosome pathway, calcium dyshomeostasis,Synucleinopathies, neuron-astrocyte co-culture |
Contact List
| Florentia Papastefanaki |
|---|
| contact affiliation | 1Human Embryonic and Induced Pluripotent Stem Cell Unit, Hellenic Pasteur Institute, Athens, Greece 2Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, Athens, Greece |
| contact email | fpapastefanaki@pasteur.gr |
| lab head | |
| Martina Samiotaki |
|---|
| contact affiliation | Protein Analysis Laboratory
B.S.R.C. "Alexander Fleming",
Alexander Fleming Street 34
16672, Vari,
Greece |
| contact email | samiotaki@fleming.gr |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD057491
- Label: PRIDE project
- Name: Proteostasis dysregulation in p.A53T--Synuclein iPSC-derived astrocytes exacerbates neurodegeneration in a Parkinson’s disease model with Lewy-like pathology
