Uric acid alleviates the inflammatory response in LPS-induced BV2 cells and MPTP-induced PD mice by resisting ferroptosis through the Nrf2 signalling pathway

作者：Dongmei Zhou, Tian Xiong, Bing Yang, Fanjie Liu, Xianglai Mo, Ting Chen, Peipei Lu, Xinghuan Liang, Li Li, Yingfen Qin, 卢德成, Feng Huang, Xi Yang · 发表于：Redox Report · 年份：2026 · DOI：10.1080/13510002.2026.2668238 · 被引用次数：1 · 研究领域：Ferroptosis and cancer prognosis、Tryptophan and brain disorders、Inflammasome and immune disorders

BACKGROUND: Neuroinflammation, oxidative stress, and ferroptosis are implicated in Parkinson' s disease (PD) pathogenesis. Epidemiological studies suggest that elevated uric acid (UA) levels may reduce PD risk, but the precise molecular mechanisms involved remain unclear. In this study, we investigated the effects of UA in lipopolysaccharide (LPS) or MPP+-stimulated BV2 microglia and MPTP-induced PD mouse models. METHODS: BV2 cells are recognized as a standardized and reproducible neural inflammatory cell model for mechanism exploration. The anti-ferroptosis and anti-inflammatory effects of UA were assessed in LPS or MPP+ stimulated BV2 microglia and in an MPTP-induced PD mouse model. Western blot, qPCR, ELISA, and immunofluorescence were used to analyse the expression of inflammasome-related markers. ROS, MDA, GSH, and Fe²⁺ levels were measured using testing kits, while mitochondrial ultrastructure was evaluated through transmission electron microscopy. PD-related markers were assessed by ethology and immunohistochemistry. The Nrf2 inhibitor ML385 was employed to validate pathway specificity. RESULTS: , IL-6, and IL-1β), ROS production, lipid peroxidation, and intracellular Fe²⁺ in BV2 microglia while increasing the antioxidant capacity and preserving the mitochondrial ultrastructure. In MPTP-treated mice, UA improved motor performance, preserved dopaminergic neuron density in the substantia nigra, and reduced neuroinflammation. UA activated Nrf2 signalling and upregulated G...