Activation of autophagy in peripheral blood mononuclear cells in amyotrophic lateral sclerosis

Abstract

Introduction.Accumulation of intracellular protein aggregatesis one of the key processes in pathogenesis of amyotrophic lateralsclerosis (ALS). Autophagy is a complex process duringwhich cell components and organelles are transferred insidelysosomes and are degraded. Autophagy disturbance was foundto take place in various neurodegenerative diseases. Autophagyalteration can be observed not only in the central nervous systembut also in peripheral blood mononuclear cells (PBMCs). Protein LC3 is the key marker of autophagy. Objective.To determine protein LC3 concentration in PBMCsof ALS patients and to analyze the relationship between thisparameter and clinical characteristics of the disease. Materials and methods.The study involved 66 patients withdefinite ALS and 15 healthy volunteers. Past medical historywas elicited in all patients; neurological examination and thepulmonary function test were performed. PBMCs were isolatedfrom blood of patients and healthy volunteers. The cells werelysed and subjected to Western blot analysis using anti-LC3 antibodies. Results.The LC3-I level in PBMCs of ALS patients was increasedcompared to that in the control group (p0.001). TheLC3-I/LC3-II level was elevated in patients with the lumbosacralform of ALS (stage II ALS and the slow rate of diseaseprogression). The tendency towards increased LC3-II level wasobserved for the bulbar form and stage III ALS. Conclusions.The results demonstrated for the first time that PBMCsof ALS patients tend to exhibit a higher level of autophagyactivity compared to healthy volunteers.

Keywords

• autophagy
• amyotrophic lateral sclerosis
• neurodegenerative diseases, biomarkers
• peripheral blood mononuclear cells