SC79 protects dopaminergic neurons from oxidative stress

Oxidative stress could lead to dopaminergic neuronal cell death. SC79 is a novel, selective and highly-efficient Akt activator. The current study tested its effect in dopaminergic neurons with oxidative stress. In both SH-SY5Y cells and primary murine dopaminergic neurons, pre-treatment with SC79 largely inhibited hydrogen peroxide (H₂O₂)-induced cell viability reduction, apoptosis and necrosis. SC79 activated Akt in the neuronal cells, which was required for its neuroprotection against H₂O₂. Inhibition of Akt activation (by MK-2206 or AT7867) or expression (by targeted short hairpin RNA) largely attenuated SC79-induced neuroprotection. Further, CRISPR-Cas9-mediated Akt1 knockout in SH-SY5Y cells abolished SC79-induced neuroprotective function against H2O2. Reversely, forced activation of Akt by the constitutively-active Akt1 mimicked SC79-induced anti-H₂O₂ activity. Together, we conclude that activation of Akt by SC79 protects dopaminergic neurons from H₂O₂.