Effect of Mutations in SOD1 and C9orf72 Genes on Autophagy in Lymphomonocytes in Myotrophic Lateral Sclerosis.

Insoluble protein inclusions accumulate in somatic cells in amyotrophic lateral sclerosis. The most common gene mutations associated with this pathology are SOD1 and C9orf72. Protein aggregates can be removed from cells by autophagy. We studied the relationship between the presence of genetic abnormalities in the SOD1 and C9orf72 genes and changes in autophagy in lymphomonocytes in amyotrophic lateral sclerosis. The study included 85 patients with amyotrophic lateral sclerosis and 15 healthy volunteers. Genetic analysis for the presence of mutations in the SOD1 and C9orf72 genes and detection of autophagy marker LC3 in lymphomonocytes were performed. In amyotrophic lateral sclerosis, autophagy activation in lymphomonocytes was found. We also obtained evidence that protein product of the mutant C9orf72 gene can disturb the late stages of autophagy.