@article{Zhao2025, 
author = {Hui Zhao and Fangyu Yan and Tianrui Zhao and Haojie Li and Tianyu Wang and Yan Li and Yuanyuan Li and Xiaofang Cheng and Yangfei Zhao and Jundong Wang and Jinming Wang},
title = {Selenium nanoparticles attenuate fluoride-induced mitophagy defect and neurotoxicity via PINK1/Parkin pathway},
year = {2025},
journal = {Food Science and Human Wellness},
keywords = {Mitophagy, Fluoride, Neurotoxicity, CS-SeNPs, Parkin},
url = {https://www.sciopen.com/article/10.26599/FSHW.2025.9250739},
doi = {10.26599/FSHW.2025.9250739},
abstract = {Prolonged exposure to fluoride can lead to neurotoxicity, which has become a global public health problem. Chitosan-selenium nanoparticles (CS-SeNPs) are high-efficiency selenium agents with low toxicity and high bioavailability that have demonstrated potential for treating neurodegenerative diseases. Nevertheless, whether CS-SeNPs ameliorate fluoride-induced neurotoxicity and the regulatory mechanisms involved remain to be clarified. Transcriptome analyses indicated that differentially expressed genes (DEGs) were predominantly enriched in cellular processes such as phagosome, cellular senescence, and mitophagy. Furthermore, the results of fluoride and/or CS-SeNPs treated E3 ubiquitin ligase Park2 (Parkin) knockout mice model indicated fluoride impeded the PTEN-induced putative kinase1 (PINK1)/Parkin-mediated mitophagy by inhibiting Parkin expression, resulting in learning and memory impairments. Conversely, CS-SeNPs supplementation rescued fluoride-induced neuronal degeneration and nuclear membrane invagination and alleviated mitochondrial ultrastructural and functional impairments. In addition, CS-SeNPs effectively promoted the clearance of damaged mitochondria and alleviated fluoride-induced neurotoxicity by up-regulation of the expression of autophagy receptors sequestosome-1 (P62), optineurin (OPTN), nuclear dot protein 52 (NDP52), and genes that regulate the formation and extension of autophagosome in the PINK1/Parkin pathway. Overall, our results suggest CS-SeNPs may be a promising candidate for alleviating fluoride-induced neurotoxicity. This provided new insights into further exploring the molecular mechanisms and therapeutic targets of fluoride neurotoxicity and also offered a new physiological function for CS-SeNPs.}
}