Idebenone improves mitochondrial respiratory activity and attenuates oxidative damage via the SIRT3-SOD2 pathway in a prion disease cell model

Abstract

Prion diseases are neurodegenerative diseases that are transmitted between humans and animals, which cause spongiform brain degeneration and neuronal death. Prion diseases are difficult to treat. Mitochondrial damage and oxidative stress occurring early in disease progression. Reducing oxidative stress is a therapeutic strategy for disease. Idebenone (IDE) is an antioxidant that enhances electron transfer in the mitochondrial respiratory chain. To investigate IDE protection mechanisms in prion neuron models, we examined IDE effects on apoptosis, mitochondrial dysfunction, cellular respiratory chain damage, and oxidative stress in N2a cells treated with the prion toxic peptide PrP^106–126. IDE effectively alleviated apoptosis and mitochondrial dysfunction, reduced mitochondrial reactive oxygen species (ROS), attenuated lipid peroxidation, improved glutathione percentages, increased important antioxidant enzyme (superoxide dismutase (SOD) and catalase) activities, and elevated mitochondrial DNA levels. IDE also modulated SOD2 deacetylation and oxidative damage by regulating SIRT3. Overall, IDE exerted significant antioxidant effects in our prion disease cell model and may have therapeutic applications for prion disease.