Neuroinflammation plays a prominent role in the pathogenesis of Parkinsons disease (PD), and microglial activation contributes to initiating and maintaining brain inflammation and neuronal death.5-Lipoxygenase (5-LOX) is a key enzyme catalyzing arachidonic acid to produce cysteinyl leukotrienes (CysLTs).CysLTs are potent proinflammatory mediators, and their actions are mediated by activating CysLT receptors.We recently reported that rotenone time-and concentration-dependently induced 5-LOX translocation into the nuclear envelope (a key event for 5-LOX activation) and cell injury in PC 12 cells, and the 5-LOX selective inhibitor zileuton attenuated rotenone-induced 5-LOX activation and cell injury.To determine the role of 5-LOX pathway in microglial-dependent neuroinflammation, we investigated the changes of 5-LOX and CysLT1 receptor in a cell model of PD induced by specific mitochondrial complex Ⅰ inhibitors (rotenone or 1-methyl-4-phenylpyridinium (MPP+)) in BV2 microglial cells.BV2 cells, a murine BV2 microglia cell line, were cultured in media with or without rotenone (0.1, 0.3, 1, 3, 10 nM) or MPP+ (0.003, 0.01, 0.03, 0.1, 0.3 μM) for 24 h.The number of microglia was counted.Phagocytotic activity of BV2 cells was evaluated using fluorescent microspheres.Expression and translocation of 5-LOX and CysLT1 receptor were detected by immunocytochemical analysis.The low doses of rotenone (1-10 nM) or MPP+ (0.03-0.3 μM) induced cell proliferation and microglial phagocytosis in BV2 cells.The number of BV2 cells was significantly increased after 24 h treatment with 1 nM rotenone or 0.03-0.1 μM MPP+.After treatment with 1-10 nM rotenone or 0.01-0.3 μM MPP+, phagocytosis was significantly increased in BV2 cells.Furthermore, we found that 5-LOX expression was increased in a time-dependent manner, and 5-LOX was primarily localized in the nuclear envelope and cytoplasm, and a plaque-like distribution was found in the nucleus in rotenone (3nM)-activated BV2 cells.In addition, MPP+ (0.003-0.3 μM) concentration-dependently induced CysLT1 receptor translocation from cell membrane to the cytoplasm.These results suggest an involvement of the 5-LOX/CysLT1 receptor in rotenone-and MPP+-induced BV2 microglial activation.The 5-LOX signaling pathway might therefore be a potential therapeutic target for modulating microglial-mediated inflammation of PD.