PXD019574

PXD019574 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling maps the molecular pathways underlying the neuroprotective effects of the kinase inhibitor BX795 in a patient-derived model of Parkinson's disease
Description	Disease-modifying therapies remain an important unmet need for neurodegenerative diseases, including Parkinson’s disease (PD). The aim of this study was to investigate the molecular pathways affected by the multi-kinase inhibitor BX795, which is neuroprotective in an induced pluripotent stem cell (iPSC)-based model of familial PD. To this end, we performed proteomics analysis in iPSC-derived neurons from patients bearing the G209A (p.A53T) α-synuclein (αSyn) mutation vis-à-vis control neurons, in the absence or presence of BX795. Comparison between p.A53T versus control neurons in the absence of BX795, revealed differential expression of 640 proteins from which only 67 were down-regulated whilst the rest 573 were up-regulated. This large increase in protein expression was linked by GO enrichment analysis mainly to the biological processes of transcription, translation, protein synthesis and modification. Upon treatment with BX795, the levels of a cohort of 118 proteins, lying mostly within these biological processes and representing approximately 20% of the total dysregulated proteins in p.A53T neurons, were restored. Enrichment analysis using the DAVID and Reactome softwares showed that these proteins are predominantly associated with mRNA metabolism, mRNA transport and translation, protein metabolism and degradation processes. This outcome was specific to p.A53T-neurons as BX795 had no significant effect on the proteome of control neurons.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:25:29.675.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: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-04 04:30:05	ID requested
1	2023-03-10 17:03:43	announced
⏵ 2	2023-11-14 08:25:30	announced	2023-11-14: Updated project metadata.

Antoniou N, Prodromidou K, Kouroupi G, Boumpoureka I, Samiotaki M, Panayotou G, Xilouri M, Kloukina I, Stefanis L, Grailhe R, Taoufik E, Matsas R, High content screening and proteomic analysis identify a kinase inhibitor that rescues pathological phenotypes in a patient-derived model of Parkinson's disease. NPJ Parkinsons Dis, 8(1):15(2022) [pubmed]

submitter keyword: proteomics, mRNA metabolism, induced pluripotent stem cell derived neurons, BX795, p.A53T α-synuclein mutation, proteostasis,α-synuclein

Rebecca Matsas
contact affiliation	Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, 11521 Athens, Greece.
contact email	rmatsa@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

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PRIDE project URI

• PRIDE
  1. PXD019574
     1. Label: PRIDE project
     2. Name: Proteomic profiling maps the molecular pathways underlying the neuroprotective effects of the kinase inhibitor BX795 in a patient-derived model of Parkinson's disease