A new strategy to uncover fragile X proteomic biomarkers using the nascent proteome of peripheral blood mononuclear cells (PBMCs).
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 07 2021
26 07 2021
Historique:
received:
29
01
2021
accepted:
05
07
2021
entrez:
27
7
2021
pubmed:
28
7
2021
medline:
4
11
2021
Statut:
epublish
Résumé
Fragile X syndrome (FXS) is the most prevalent inherited cause of intellectual disabilities and autism spectrum disorders. FXS result from the loss of expression of the FMRP protein, an RNA-binding protein that regulates the expression of key synaptic effectors. FXS is also characterized by a wide array of behavioural, cognitive and metabolic impairments. The severity and penetrance of those comorbidities are extremely variable, meaning that a considerable phenotypic heterogeneity is found among fragile X individuals. Unfortunately, clinicians currently have no tools at their disposal to assay a patient prognosis upon diagnosis. Since the absence of FMRP was repeatedly associated with an aberrant protein synthesis, we decided to study the nascent proteome in order to screen for potential proteomic biomarkers of FXS. We used a BONCAT (Biorthogonal Non-canonical Amino Acids Tagging) method coupled to label-free mass spectrometry to purify and quantify nascent proteins of peripheral blood mononuclear cells (PBMCs) from 7 fragile X male patients and 7 age-matched controls. The proteomic analysis identified several proteins which were either up or downregulated in PBMCs from FXS individuals. Eleven of those proteins were considered as potential biomarkers, of which 5 were further validated by Western blot. The gene ontology enrichment analysis highlighted molecular pathways that may contribute to FXS physiopathology. Our results suggest that the nascent proteome of PBMCs is well suited for the discovery of FXS biomarkers.
Identifiants
pubmed: 34312401
doi: 10.1038/s41598-021-94027-5
pii: 10.1038/s41598-021-94027-5
pmc: PMC8313568
doi:
Substances chimiques
Biomarkers
0
Blood Proteins
0
Proteome
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15148Informations de copyright
© 2021. The Author(s).
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