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

Introduction. Accumulation of intracellular protein aggregates is one of the key processes in pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is a complex process during which cell components and organelles are transferred inside lysosomes and are degraded. Autophagy disturbance was found to take place in various neurodegenerative diseases. Autophagy alteration can be observed not only in the central nervous system but also in peripheral blood mononuclear cells (PBMCs). Protein LC3 is the key marker of autophagy.
Objective. To determine protein LC3 concentration in PBMCs of ALS patients and to analyze the relationship between this parameter and clinical characteristics of the disease.
Materials and methods. The study involved 66 patients with definite ALS and 15 healthy volunteers. Past medical history was elicited in all patients; neurological examination and the pulmonary function test were performed. PBMCs were isolated from blood of patients and healthy volunteers. The cells were lysed and subjected to Western blot analysis using anti-LC3 antibodies.
Results. The LC3-I level in PBMCs of ALS patients was increased compared to that in the control group (p<0.001). The LC3-I/LC3-II level was elevated in patients with the lumbosacral form of ALS (stage II ALS and the slow rate of disease progression). The tendency towards increased LC3-II level was observed for the bulbar form and stage III ALS.
Conclusions. The results demonstrated for the first time that PBMCs of ALS patients tend to exhibit a higher level of autophagy activity compared to healthy volunteers.