Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.

<h4>Background</h4>Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability and is caused by the loss of expression of the Fragile X mental retardation protein (FMRP). In animal model of FXS, the absence of FMRP leads to an aberrant rate of neuronal protein synt...

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Autores principales:	Olivier Dionne, Audrey Lortie, Florence Gagnon, François Corbin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f572dc4e2a994ddb92ab37387e58176a
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spelling	oai:doaj.org-article:f572dc4e2a994ddb92ab37387e58176a2021-12-02T20:11:20ZRates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.1932-620310.1371/journal.pone.0251367https://doaj.org/article/f572dc4e2a994ddb92ab37387e58176a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251367https://doaj.org/toc/1932-6203<h4>Background</h4>Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability and is caused by the loss of expression of the Fragile X mental retardation protein (FMRP). In animal model of FXS, the absence of FMRP leads to an aberrant rate of neuronal protein synthesis, which in turn is believed to be at the origin of defects regarding spine morphology and synaptic plasticity. Normalisation of protein synthesis in these models has been associated with a rescue of FXS behavioral and biochemicals phenotype, thus establishing the rate of protein synthesis as one of the most promising monitoring biomarker for FXS. However, rate of protein synthesis alteration in fragile X individuals is not well characterized.<h4>Method</h4>We applied a robust radiolabeled assay to measure rate of protein synthesis in freshly extracted peripheral blood mononuclear cells (PBMCs) and blood platelets. We ultimately settle on PBMCs to measure and compare rate of protein synthesis in 13 males with fragile X and 14 matched controls individuals.<h4>Results</h4>Using this method, we measured a 26.9% decrease (p = 0,0193) in the rate of protein synthesis in fragile X individuals PBMCs. Furthermore, the rate of protein synthesis measurements obtained were highly reproducible, highlighting the robustness of the method.<h4>Conclusion</h4>Our work presents the first evidence of a diminution of the rate of protein synthesis in a human peripheral model of fragile X. Our results also support the finding of previous studies using brain PET imaging in Fragile X individuals. Since our assay only requires a simple venous puncture, it could be used in other cases of intellectual disability in order to determine if an aberrant rate of protein synthesis is a common general mechanism leading to impairment in synaptic plasticity and to intellectual disability.Olivier DionneAudrey LortieFlorence GagnonFrançois CorbinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251367 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olivier Dionne Audrey Lortie Florence Gagnon François Corbin Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.
description	<h4>Background</h4>Fragile X syndrome (FXS) is the leading inherited cause of intellectual disability and is caused by the loss of expression of the Fragile X mental retardation protein (FMRP). In animal model of FXS, the absence of FMRP leads to an aberrant rate of neuronal protein synthesis, which in turn is believed to be at the origin of defects regarding spine morphology and synaptic plasticity. Normalisation of protein synthesis in these models has been associated with a rescue of FXS behavioral and biochemicals phenotype, thus establishing the rate of protein synthesis as one of the most promising monitoring biomarker for FXS. However, rate of protein synthesis alteration in fragile X individuals is not well characterized.<h4>Method</h4>We applied a robust radiolabeled assay to measure rate of protein synthesis in freshly extracted peripheral blood mononuclear cells (PBMCs) and blood platelets. We ultimately settle on PBMCs to measure and compare rate of protein synthesis in 13 males with fragile X and 14 matched controls individuals.<h4>Results</h4>Using this method, we measured a 26.9% decrease (p = 0,0193) in the rate of protein synthesis in fragile X individuals PBMCs. Furthermore, the rate of protein synthesis measurements obtained were highly reproducible, highlighting the robustness of the method.<h4>Conclusion</h4>Our work presents the first evidence of a diminution of the rate of protein synthesis in a human peripheral model of fragile X. Our results also support the finding of previous studies using brain PET imaging in Fragile X individuals. Since our assay only requires a simple venous puncture, it could be used in other cases of intellectual disability in order to determine if an aberrant rate of protein synthesis is a common general mechanism leading to impairment in synaptic plasticity and to intellectual disability.
format	article
author	Olivier Dionne Audrey Lortie Florence Gagnon François Corbin
author_facet	Olivier Dionne Audrey Lortie Florence Gagnon François Corbin
author_sort	Olivier Dionne
title	Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.
title_short	Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.
title_full	Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.
title_fullStr	Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.
title_full_unstemmed	Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.
title_sort	rates of protein synthesis are reduced in peripheral blood mononuclear cells (pbmcs) from fragile x individuals.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f572dc4e2a994ddb92ab37387e58176a
work_keys_str_mv	AT olivierdionne ratesofproteinsynthesisarereducedinperipheralbloodmononuclearcellspbmcsfromfragilexindividuals AT audreylortie ratesofproteinsynthesisarereducedinperipheralbloodmononuclearcellspbmcsfromfragilexindividuals AT florencegagnon ratesofproteinsynthesisarereducedinperipheralbloodmononuclearcellspbmcsfromfragilexindividuals AT francoiscorbin ratesofproteinsynthesisarereducedinperipheralbloodmononuclearcellspbmcsfromfragilexindividuals
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Rates of protein synthesis are reduced in peripheral blood mononuclear cells (PBMCs) from fragile X individuals.

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