Beneficial Antioxidant Effects of Coenzyme Q10 in In Vitro and In Vivo Models of CDKL5 Deficiency Disorder.

deficiency disorder (CDD), a developmental encephalopathy caused by mutations in the cyclin-dependent kinase-like 5 () gene, is characterized by a complex and severe clinical picture, including early-onset epilepsy and cognitive, motor, visual, and gastrointestinal disturbances. This disease still lacks a medical treatment to mitigate, or reverse, its course and improve the patient's quality of life. Although CDD is primarily a genetic brain disorder, some evidence indicates systemic abnormalities, such as the presence of a redox imbalance in the plasma and skin fibroblasts from CDD patients and in the cardiac myocytes of a mouse model of CDD. In order to shed light on the role of oxidative stress in the CDD pathophysiology, in this study, we aimed to investigate the therapeutic potential of Coenzyme Q10 (CoQ10), which is known to be a powerful antioxidant, using in vitro and in vivo models of CDD. We found that CoQ10 supplementation not only reduces levels of reactive oxygen species (ROS) and normalizes glutathione balance but also restores the levels of markers of DNA damage (γ-H2AX) and senescence (lamin B1), restoring cellular proliferation and improving cellular survival in a human neuronal model of CDD. Importantly, oral supplementation with CoQ10 exerts a protective role toward lipid peroxidation and DNA damage in the heart of a murine model of CDD, the (+/-) female mouse. Our results highlight the therapeutic potential of the antioxidant supplement CoQ10 in counteracting the detrimental oxidative stress induced by CDKL5 deficiency.