Activation of caspase-3 and c-Jun NH2-terminal kinase signaling pathways involving heroin-induced neuronal apoptosis

► Heroin has been shown to cause spongiform leukoencephalopathy in addicts who had a history of inhaling heated heroin vapor. ► We demonstrate that cerebellar granule cells (CGC) die when maintained in heroin. ► Heroin triggers CGCs die via apoptosis. Heroin-induced apoptosis is dependent on caspase-3 activation and JNK/c-Jun lie upstream of caspase-3 in a cascade. ► JNK pathway and caspases are contributed to heroin-induced neuronal cell death in CGCs. ► These results may represent a new and effective strategy to treat heroin-induced spongiform leukoencephalopathy.