Prevention of Glutamate-Induced Neurodegeneration by Piceatannol Via Mitochondrial Rescue in Vitro and in Vivo.

Abstract

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. The PC12 cell line and three Caenorhabditis elegans (C. elegans) strains were employed to achieve our aim. In the in vitro study, our results showed that piceatannol could prevent glutamate-induced apoptosis. Piceatannol also reduced mitochondrial reactive oxygen species (ROS) accumulation by activating the antioxidant system via Nrf2/HO-1 and SOD. Moreover, piceatannol could also promote mitochondrial biogenesis via the PGC1α/NRF1/TRAM/SIRT3 pathway and induced mitochondrial fusion-related genes, including Mfn1, Mfn2, and Opa1, to preserve mitochondrial functionality. In the C. elegans model, piceatannol could prevent mitochondrial fragmentation induced by glutamate. More importantly, piceatannol effectively protected dopaminergic neurons from degradation and preserved the responses controlled by these neurons. Our 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. This article is protected by copyright. All rights reserved.