Proteomics analysis of the p.G849D variant in neurexin 2 alpha may reveal insight into Parkinson’s disease pathobiology
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Date
2022
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Publisher
Frontiers
Abstract
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
were then interrogated against the UniProt H. sapiens database and afterward,
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
Description
Keywords
parkinson’s disease, proteomics, mass spectrometry, synaptic translation, mitochondrial dysfunction
Citation
Cuttler, K., Fortuin, S., Müller-Nedebock, A.C., Vlok, M., Cloete, R., Bardien, S., 2022. Proteomics analysis of the p.G849D variant in neurexin 2 alpha may reveal insight into Parkinson’s disease pathobiology. Frontiers in Aging Neuroscience.14, 1002777. https://doi.org/10.3389/fnagi.2022.1002777