Accumulation of amyloid-β(Aβ)is thought to associate with the progressive neuronal death observed in Alzheimers disease(AD),but the mechanisms underlying neurotoxicity triggered by Aβ remains elusive.In the present study,we investigated the roles of cysteinyl leukotriene receptor 1(CysLT1R)in Aβ1-42-induced neurotoxicity in vitro or in vivo.In vitro exposure of mouse primary neurons to Aβ1-42 caused gradual increases in CysLT1R expression.In vivo bilateral intrahippocampal injection of Aβ1-42 also elicited timedependent increases of CysLT1R expression in either hippocampus or cortex of mice.CysLT1R antagonist pranlukast not only reversed Aβ1-42-induced upregulation of CysLT1R,but also suppressed Aβ1-42-triggered neurotoxicity evidenced by increased NF-κB p65,activated caspase-3,decreased Bcl-2,reduced cellular viability and impaired memory.Furthermore,chronic treatment with pranlukast produced similar beneficial effects on memory behavior and hippocampal LTP to memantine or donepezil in intrahippocampal Aβ1-42-injected mice.Our data indicate that CysLT1R is involved in Aβ1-42-induced neurotoxicity and blockade of CysLT1R,such as application of CysLT1R antagonist,could be a novel and promising strategy for treatment of AD.