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

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.