Prevention of Glutamate‐Induced Neurodegeneration by Piceatannol via Mitochondrial Rescue In Vitro and In Vivo

Abstract

Scope Parkinson's disease is one of the neurodegenerative diseases that have no cure. Excitotoxicity induced by excess glutamate is known to be a hallmark of these diseases. Therefore, this study aims to evaluate the preventive effect of piceatannol on glutamate‐induced neurodegeneration via mitochondrial rescue. Methods and results The PC12 cell line and three Caenorhabditis elegans (C. elegans) strains are employed to achieve the aim. In the in vitro study, the results show that piceatannol can prevent glutamate‐induced apoptosis. Piceatannol also reduces mitochondrial reactive oxygen species (ROS) accumulation by activating the antioxidant system. Moreover, piceatannol can also promote mitochondrial biogenesis and induced mitochondrial fusion‐related genes to preserve mitochondrial functionality. In the C. elegans model, piceatannol can prevent mitochondrial fragmentation induced by glutamate. More importantly, piceatannol effectively protects dopaminergic neurons from degradation and preserves the responses controlled by these neurons. Conclusion The findings suggest that piceatannol can be a more effective and potent candidate for the treatment of neurodegenerative diseases, such as Parkinson's disease, compared to resveratrol. It is capable of preventing neurodegeneration induced by excess glutamate, possibly via mitochondrial rescue. It is recommended that piceatannol be developed into a neuroprotective agent.