PXD036636

PXD036636 is an original dataset announced via ProteomeXchange.

Title	Proteomics analysis of the p.G849D variant in neurexin 2 alpha may reveal insight into Parkinson’s disease pathobiology
Description	Parkinson’s disease (PD), the fastest growing neurological disorder globally, has a complex etiology. A previous study by our group identified the p.G849D variant in neurexin 2 (NRXN2), encoding the synaptic protein, NRXN2α, as a possible causal variant of PD. Therefore, we aimed to perform functional studies using proteomics in an attempt to understand the biological pathways affected by the variant. We hypothesized that this may reveal insight into the pathobiology of PD. Wild-type and mutant NRXN2α plasmids were transfected into SH-SY5Y cells. Thereafter, total protein was extracted and prepared for mass spectrometry using a Thermo Scientific Fusion mass spectrometer equipped with a Nanospray Flex ionization source. The data was then interrogated against the UniProt H. sapiens database and afterwards, pathway and enrichment analyses were performed using in silico tools. Overexpression of the wild-type protein led to the enrichment of proteins involved in neurodegenerative diseases, while overexpression of the mutant protein led to the decline of proteins involved in ribosomal functioning. Thus, we concluded that the wild-type NRXN2α may be involved in pathways related to the development of neurodegenerative disorders, and that biological processes related to the ribosome, transcription and tRNA, specifically at the synapse, could be an important mechanism in PD. Future targeted studies translation at the synapse in PD could therefore provide further information on the pathobiology of the disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:42:58.018.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD036636
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Katelyn Cuttler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-12 05:23:41	ID requested
1	2023-03-11 05:32:28	announced
⏵ 2	2023-11-14 08:42:58	announced	2023-11-14: Updated project metadata.

10.6019/PXD036636;

Cuttler K, Fortuin S, M, ü, ller-Nedebock AC, Vlok M, Cloete R, Bardien S, Proteomics analysis of the p.G849D variant in neurexin 2 alpha may reveal insight into Parkinson's disease pathobiology. Front Aging Neurosci, 14():1002777(2022) [pubmed]

submitter keyword: pG849D, mitochondrial dysfunction, ribosomal functioning,neurexin 2α (NRXN2), Parkinson’s disease, synaptic translation

Soraya Bardien
contact affiliation	Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
contact email	sbardien@sun.ac.za
lab head
Katelyn Cuttler
contact affiliation	Stellenbosch University
contact email	kcuttler@sun.ac.za
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD036636

PRIDE project URI

• PRIDE
  1. PXD036636
     1. Label: PRIDE project
     2. Name: Proteomics analysis of the p.G849D variant in neurexin 2 alpha may reveal insight into Parkinson’s disease pathobiology