Novel role of curcumin as inhibitor of β-amyloid-induced lamin fragmentation

Oligomer amyloid beta 42 (A beta) is considered the key pathogenic molecule in Alzheimer disease (AD) and causes specific lamin fragmentation. Curcumin has been recognized for its protective effects against A beta-induced toxicity in AD, though its underlying mechanism remains unclear. In this study, the inhibitory mechanism of curcumin against A beta-induced lamin fragmentation and cell death was investigated. Human neuroblastoma cells were used to examine A beta-induced lamin fragmentation and lamin deformation by immunoblotting and confocal microscopy, while cell viability was measured using MTT and alamarBlue assay. Caspase and cathepsin L activity were assessed by spectrofluorometry, and A beta aggregation was evaluated by ThT assay. Our results demonstrated that curcumin inhibited A beta aggregation, reducing intracellular A beta uptake by 45% compared to A beta-treated cells. Curcumin also inhibited the A beta-induced intracellular calcium rise, subsequently leading to a onefold reduction in cathepsin L activity. This reduction in cathepsin L activity by curcumin blocked the A beta-induced lamin fragmentation. Collectively, these findings suggest that curcumin inhibits A beta-induced cell death by preventing A beta entry and lamin cleavage, providing potential new insights for AD treatment.