Abstract
Neurodegenerative diseases are major global health problems with increasing incidence rates. A large amount of data suggests that excitotoxicity is a potential target of neurodegenerative diseases. However, effective pharmacological interventions against excitotoxicity are lacking. We aimed to elucidate the neuroprotective effect and mechanism of the mitochondrion-targeted NOX inhibitor mito-apocynin on kainic acid (KA)-induced excitotoxicity. We found that KA impaired mitochondrial morphology and led to impaired mitochondrial energy metabolism and dysfunction. In Western blotting experiments, KA disrupted mitochondrial quality control. In Nissl staining and CCK8 experiments, Mito-apocynin attenuated the death of neurons due to excitotoxic damage induced by KA both in vivo and in vitro. Mito-apocynin ameliorated neurobehavior induced by KA deficits in vivo and mitochondrial dysfunction in vitro. Mito-apocynin significantly reversed the increase in NOX4 levels caused by KA in the mitochondria of the striatum, decreased phosphorylated DRP1 (Ser616)/total DRP1 and increased PGC-1α, PINK1 and Parkin protein expression in the total striatum. In summary, Mito-apocynin alleviated oxidative stress, maintained normal mitochondrial function and energy metabolism levels, and promoted the balance of mitochondrial quality control by regulating the expression of NOX in mitochondria, thus reducing KA-induced excitatory toxic damage.