OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase(5-LOX)inhibitor as well as cysteinyl leukotriene receptor 1(Cys LT1)antagoniston rotenone-induced microglial activation and neuronal death.In this study,we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine(MPP+)in an in vitro model of Parkinson disease(PD).METHODS The neurotoxicity of MPP+,a neurotoxin relevant to PD,on the PC12 cells was measured by MTT assay,lactate dehydrogenase(LDH)release and double fluorescence staining with Hoechst/propidiumiodide(PI).The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods.RESULTS We found that exposure of PC12 cells to MPP+led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner.Pretreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP+-treated PC12 cells.Furthermore,MPP+increasednecrotic cell death in PC12 cells.Administration of montelukast significantly decreased MPP+-induced cell necrosis in PC12 cells.CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP+-induced neurotoxicity in PC12 cells.The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders. OBJECTIVE Previously we demonstrated the neuroprotective effect of 5-lipoxygenase (5-LOX) inhibitor as well as cysteinyl leukotriene receptor 1 (Cys LT1) antagoniston rotenone-induced microglial activation and neuronal death. In this study, we determined the effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast on neurotoxicity induced by 1-methyl-4-phenylpyridine (MPP +) in an in vitro model of Parkinson disease (PD). METHODS The neurotoxicity of MPP +, a neurotoxin relevant to PD, on the PC12 cells was measured by MTT assay, lactate dehydrogenase (LDH) release and double fluorescence staining with Hoechst / propidiumiodide (PI). The protective effects of 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast were investigated by the above methods. PC12 cells to MPP + led to a reduced cell viability and an increased level of LDH in a concentration-dependent manner. Petreatment with zileuton and montelukast significantly attenuated viability loss and LDH release in MPP + -treated PC12 cells. Thermoremore, MPP + increasednecrotic cell death in PC12 cells. Administration of montelukast significantly decreased MPP + -induced cell necrosis in PC12 cells. CONCLUSION The 5-LOX inhibitor zileuton and Cys LT1 antagonist montelukast have a neuroprotective effects on MPP + -induced neurotoxicity in PC12 cells. The 5-LOX inhibitor and Cys LT1 antagonist might raise a possibility as potential therapeutic agent for PD and other inflammation-related the central nervous system disorders.