γ-L-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-L-cysteinylglycine sodium salt (ESeroS-GS) is a water-soluble derivative ofα-tocopherol(vitamin E).We reported previous thatESeroS-GScan act as an anti-inflammatory agent and can induce cell death in breast cancer cells.However,the potential antioxidant capacities of ESeroS-GSremain elusive.Here,we measured its scavenging effects on free radicals and evaluated its protective effects on neuronal cellsagainst oxidative stress.The results indicated that ESeroS-GS effectively scavenged both ABTS·+ and DPPH free radicals,and attenuatedH2O2-induced neuronalcell death.H2O2treatmentinduced lysosomal membrane permeabilization rapidly,and caused the redistribution of lysosomal proteases,which was responsible for the neuronal cell death.ESeroS-GS abolished the interaction between tBid and the lysosomal membranes,blocked the translocation of tBid to the lysosomal membranes,decreased its oligomerization within the membrane circumstances,prevented the lysosomal membrane permeabilization,and thus attenuated the neuronal cell death.These data suggests that ESeroS-GS protected the neuronal cells from oxidative stress by stabilizing lysosomal membranes,and thus might act as a novel neuroprotector for neuronal diseasesassociated with oxidative stress.