Curcumin enhanced cell viability and attenuated LPS-challenge-driven cell death in non-stressed and LPS-challenged neural cells. The knockdown of CISD2 expression was shown to reduce the protective effects of curcumin. The eight groups of cells included the following: (i) scrambled RNA-transfected control cells, untreated with LPS and curcumin; (ii) scrambled RNA-transfected cells treated with curcumin; (iii) scramble RNA-transfected, LPS-challenged cells, without curcumin treatment; (iv) scramble RNA-transfected, LPS-challenged cells treated with curcumin; (v) siCID2-transfected control cells without LPS or curcumin treatment; (vi) siCID2-transfected cells treated with curcumin; (vii) siCID2-transfected, LPS-challenged cells without curcumin treatment; (viii) siCID2-transfected, LPS-challenged cells, treated with curcumin. Cell viability was measured using alamarBlue® assay. Vertical bars indicate the mean ± SEM (n = 3). #,&,* p < 0.05, &&,** p < 0.01, and ###,*** p < 0.001 indicate differences of statistical significance.