Lack of synucleins induces an alteration of lipid peroxidation in the brain.

Abstract

Family proteins - α-, β, γ-synucleins shown to play important roles in metabolism, signal transduction and dopamine handling. Aggregated α-synuclein is neurotoxic and involved in pathogenesis of Parkinson's disease. The mechanism toxicity of aggregated α-synuclein includes lipid peroxidation, oxidative stress and ferroptosis but effect of monomeric synucleins on the basal lipid peroxidation is unclear. Using acute brain slices and primary cortical co-culture of neurons and astrocytes from α-, β- and γ-synuclein deficient mice and live cell imaging we studied how lack of synucleins changes the rate of lipid peroxidation and level of reduced glutathione (GSH) in basal conditions and under dopamine treatment. We have found that lack of synucleins leads to significant reduction in the basal rate of lipid peroxidation and dopamine-induced further decrease of lipid peroxidation in these brain slices. The level of GSH in neurons and astrocytes with synuclein deficiency was higher or similar to wild type cells, the level of NADPH and rate of NADH production also were unchanged. Thus, synuclein deficiency induces alteration of process of lipid peroxidation in brain cells independently of oxidative stress.