Glycogen Synthase Kinase-3β Expression and Phosphorylation in Peripheral Blood Mononuclear Cells of Patients with Amyotrophic Lateral Sclerosis

Miguel González-Muñoz *

ALS Unit, Hospital Carlos III, Sinesio Delgado 10, 28029, Madrid, Spain and Department of Immunology, Hospital Carlos III, Sinesio Delgado 10, 28029, Madrid, Spain.

Ana I. Rodríguez-Mahillo

Fundación para la Investigación Biomédica, Sinesio Delgado 10, 28029, Madrid, Spain.

Carmen Gil

Instituto de Química Médica-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.

Yolanda Morán

ALS Unit, Hospital Carlos III, Sinesio Delgado 10, 28029, Madrid, Spain.

Ignacio Moneo

Department of Immunology, Hospital Carlos III, Sinesio Delgado 10, 28029, Madrid, Spain.

Ana Martínez

Instituto de Química Médica-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.

Jesús S. Mora

ALS Unit, Hospital Carlos III, Sinesio Delgado 10, 28029, Madrid, Spain.

*Author to whom correspondence should be addressed.


Abstract

Aims: To quantify total glycogen synthase kinase (GSK)-3β and GSK-3β phosphorylated at serine 9 in the peripheral blood mononuclear cells from Amyotrophic Lateral Sclerosis (ALS) patients and to assess if GSK-3β could be a biomarker for ALS.
Study Design: Cross-sectional observational study.
Place and Duration of Study: Department of Immunology and Amyotrophic Lateral Sclerosis Unit, Hospital Carlos III, Madrid, Spain, between February 2011 and August 2012.
Methodology: Blood samples were drawn from 44 ALS patients and 41 healthy controls. Peripheral blood mononuclear cells were isolated and cellular extracts were obtained to assess GSK-3β and serine 9 phosphorylated GSK-3β concentrations. Enzymes were measured by a quantitative enzyme-linked immunoassay in the peripheral blood mononuclear cell extracts. Patients were divided into two groups according to the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) median value for the comparative analysis.
Results: Patients (n=22) showing a high functional impairment (ALSFRS-R ≤ 32) had GSK-3β levels (11.2±3.6 pg/μg protein) higher than healthy controls (8.7±4.7 pg/μg protein; P=0.04) and than those patients (n=22) with ALSFRS-R > 32 (6.9±4.4 pg/μg protein; P<0.01). A negative correlation between GSK-3β concentration and ALSFRS-R values (r = −0.39; P=0.006) was also observed.
Conclusion: Our results show that GSK-3β expression is altered in non-neural cells of ALS patients and suggest that its overexpression may play a role in the pathogenesis of ALS. The quantification of GSK-3β in peripheral blood mononuclear cells may be used as a potential biomarker of ALS progression.

Keywords: Amyotrophic lateral sclerosis, glycogen synthase kinase-3β, peripheral blood mononuclear cells, biomarker.


How to Cite

González-Muñoz, M., I. Rodríguez-Mahillo, A., Gil, C., Morán, Y., Moneo, I., Martínez, A., & S. Mora, J. (2013). Glycogen Synthase Kinase-3β Expression and Phosphorylation in Peripheral Blood Mononuclear Cells of Patients with Amyotrophic Lateral Sclerosis. Journal of Advances in Medicine and Medical Research, 4(1), 263–271. https://doi.org/10.9734/BJMMR/2014/5578

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