Curcumin has been reported to have a therapeutic effect on Alzheimer’s disease (AD), but the specific mechanism remains to be elucidated. In the present research, we aimed to investigate the effect and molecular mechanism of curcumin on AD. Mouse primary hippocampal neuron cells were treated with various concentrations of beta-amyloid 42 (Aβ₄₂) and the results found that Aβ₄₂ inhibited cell viability in a dose-dependent manner. Compared with 50 ng/mL Aβ₄₂, 500 ng/mL Aβ₄₂ could further promote cell apoptosis, reduce the ratio of Nicotinamide adenine dinucleotide (NAD(+))/Nicotinamide adenine diphosphate hydride (NADH) and Adenosine 5′-triphosphate (ATP) level, and inhibit Sirtuins 3 (SIRT3) deacetylation activity and protein expression of Thyroid hormone receptor beta (Thrb) and SIRT3. Hence, 500 ng/mL Aβ₄₂ was used to establish a cell model of AD. Curcumin significantly reversed the inhibitory effects of Aβ₄₂ on cell viability, SIRT3 deacetylation activity, the ratio of NAD⁺/NADH, ATP level and the protein expression of Thrb and SIRT3, and the promotive effect on apoptosis. ChIPBase was used to predict the binding region of Thrb and SIRT3. Dual luciferase reporter gene and Chromatin immune precipitation (ChIP) assays were employed to verify the relationship between Thrb and promoter of SIRT3 mRNA. Overexpression of Thrb recovered Aβ₄₂ induced metabolic dysfunction, while Thrb silence aggravated Aβ₄₂ induced metabolic dysfunction. Moreover, Thrb silence or 3-TYP (a selective inhibitor of SIRT3) treatment abolished the amelioration of curcumin on Aβ₄₂ induced metabolic dysfunction. Additionally, curcumin attenuated memory deficits in Amyloid precursor protein transgenic (APP_TG) mice. Collectively, curcumin alleviated Aβ₄₂-induced neuronal metabolic dysfunction through increasing Thrb expression and SIRT3 activity and improved cognition in APP_TG mice.

据报道姜黄素对阿尔茨海默病 (AD) 有治疗作用，但具体机制仍有待阐明。在本研究中，我们旨在研究姜黄素对 AD 的作用及其分子机制。用不同浓度的 β-淀粉样蛋白 42 (Aβ ₄₂ ) 处理小鼠原代海马神经元细胞，结果发现 Aβ ₄₂以剂量依赖性方式抑制细胞活力。与 50 ng/mL Aβ ₄₂、500 ng/mL Aβ _42相比可进一步促进细胞凋亡，降低烟酰胺腺嘌呤二核苷酸（NAD（+））/烟酰胺腺嘌呤二磷酸氢化物（NADH）和腺苷5'-三磷酸（ATP）水平，抑制Sirtuins 3（SIRT3）去乙酰化活性和蛋白表达甲状腺激素受体 β (Thrb) 和 SIRT3。因此，使用 500 ng/mL Aβ ₄₂建立 AD 细胞模型。姜黄素显着逆转 Aβ ₄₂对细胞活力、SIRT3 去乙酰化活性、NAD ^{+比值的抑制作用}/NADH、ATP 水平和 Thrb 和 SIRT3 的蛋白表达，以及对细胞凋亡的促进作用。ChIPBase 用于预测 Thrb 和 SIRT3 的结合区域。采用双荧光素酶报告基因和染色质免疫沉淀 (ChIP) 测定来验证 Thrb 与 SIRT3 mRNA 启动子之间的关系。Thrb的过表达恢复了Aβ ₄₂诱导的代谢功能障碍，而Thrb沉默加重了Aβ ₄₂诱导的代谢功能障碍。此外，Thrb 沉默或 3-TYP（SIRT3 的选择性抑制剂）治疗消除了姜黄素对 Aβ ₄₂诱导的代谢功能障碍的改善作用。此外，姜黄素可减轻淀粉样前体蛋白转基因（APP _TG） 老鼠。总的来说，姜黄素通过增加 Thrb 表达和 SIRT3 活性来缓解 Aβ ₄₂诱导的神经元代谢功能障碍，并改善 APP _TG小鼠的认知。