INTRODUCTION: Superoxide dismutase 1 (SOD1) binds Cu/Zn and is located in the cytoplasm. It is one of three enzymes of a family of SODs which catalyse the dismutation reaction of superoxide to hydrogen peroxide. Mutations of the SOD1 in humans lead to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder that is characterized by the progressive injury of motor neurons. Under pathological conditions, hSOD1 variants go through changes in conformation, leading to protein misfolding and the formation of neurotoxic aggregates. By expressing the hSOD1 gene within the Drosophila melanogaster nervous system, we can observe how the molecular changes cause the declines in lifespan and fitness.

AIM(S): The aim of the study was to investigate the effects of pan-neuronal expression of human superoxide dismutase 1 gene on the survival and fitness of Drosophila melanogaster.

METHOD(S): Pan-neuronal expression of hSOD1 was achieved using the UAS-Gal4 system by crossing elav-Gal4 (driver) and UAS-hSOD1 (responder) lines. Controls were established by crossing both lines to a w1118 (white) background. The transgenic flies were kept on a standard cornmeal medium. Survival was monitored every day. Flies were transferred to a fresh medium twice per week. Fitness was evaluated by the negative geotaxis assays on 7, 15, 30, and 50 day old flies. Flies were tapped to the bottom of empty vials under dim red light. The number of individuals crossing the threshold (12,5 cm) within 15s was recorded. The test was repeated 3 times per group/sex.

RESULTS: The negative geotaxis assay showed a decrease in the fitness of both sexes of the transgenic flies with age.

CONCLUSIONS: Expression of the human Cu/Zn superoxide dismutase gene in Drosophila melanogaster neurons affects their survival and fitness.

FINANCIAL SUPPORT: NCN project nr 2020/39/B/NZ7/03366