Hossain Md Selim, Haque Md Aminul, Park Il-Seon
Department of Biomedical Sciences, Chosun University, Gwangju, 61452, Republic of Korea.
Department of Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA.
Histochem Cell Biol. 2024 Nov 14;163(1):2. doi: 10.1007/s00418-024-02331-8.
Oligomer amyloid beta 42 (Aβ) is considered the key pathogenic molecule in Alzheimer disease (AD) and causes specific lamin fragmentation. Curcumin has been recognized for its protective effects against Aβ-induced toxicity in AD, though its underlying mechanism remains unclear. In this study, the inhibitory mechanism of curcumin against Aβ-induced lamin fragmentation and cell death was investigated. Human neuroblastoma cells were used to examine Aβ-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 Aβ aggregation was evaluated by ThT assay. Our results demonstrated that curcumin inhibited Aβ aggregation, reducing intracellular Aβ uptake by 45% compared to Aβ-treated cells. Curcumin also inhibited the Aβ-induced intracellular calcium rise, subsequently leading to a onefold reduction in cathepsin L activity. This reduction in cathepsin L activity by curcumin blocked the Aβ-induced lamin fragmentation. Collectively, these findings suggest that curcumin inhibits Aβ-induced cell death by preventing Aβ entry and lamin cleavage, providing potential new insights for AD treatment.
寡聚淀粉样β蛋白42（Aβ）被认为是阿尔茨海默病（AD）的关键致病分子，并会导致特定的核纤层断裂。姜黄素因其对AD中Aβ诱导的毒性具有保护作用而受到认可，但其潜在机制仍不清楚。在本研究中，研究了姜黄素对Aβ诱导的核纤层断裂和细胞死亡的抑制机制。使用人神经母细胞瘤细胞通过免疫印迹和共聚焦显微镜检查Aβ诱导的核纤层断裂和核纤层变形，同时使用MTT和alamarBlue测定法测量细胞活力。通过荧光分光光度法评估半胱天冬酶和组织蛋白酶L的活性，并通过硫代黄素T测定法评估Aβ聚集。我们的结果表明，姜黄素抑制Aβ聚集，与Aβ处理的细胞相比，细胞内Aβ摄取减少45%。姜黄素还抑制Aβ诱导的细胞内钙升高，随后导致组织蛋白酶L活性降低一倍。姜黄素对组织蛋白酶L活性的这种降低阻止了Aβ诱导的核纤层断裂。总的来说，这些发现表明姜黄素通过防止Aβ进入和核纤层切割来抑制Aβ诱导的细胞死亡，为AD治疗提供了潜在的新见解。
