Alzheimer’s disease (AD) is a neurodegenerative disease representing the most prevalent cause of dementia. It is also related to the aberrant amyloid-beta (Aβ) protein deposition in the brain. Since oxidative stress is involved in AD, there is a possible role of antioxidants present in the effected person’s diet. Thus, we assessed the effect of the systemic administration of solid lipid nanoparticles (SLNs) to facilitate curcumin (CUR) delivery on TG2 isoform expression levels in Wild Type (WT) and in TgCRND8 (Tg) mice. An experimental model of AD, which expresses two mutated human amyloid precursor protein (APP) genes, was used. Behavioral studies were also performed to evaluate the improvement of cognitive performance and memory function induced by all treatments. The expression levels of Bcl-2, Cyclin-D₁, and caspase-3 cleavage were evaluated as well. In this research, for the first time, we demonstrated that the systemic administration of SLNs-CUR, both in WT and in Tg mice, allows one to differently modulate TG2 isoforms, which act either on apoptotic pathway activation or on the ability of the protein to repair cellular damage in the brains of Tg mice. In this study, we also suggest that SLNs-CUR could be an innovative tool for the treatment of AD.

中文翻译：

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在阿尔茨海默病的实验模型中，未加载和加载姜黄素的固体脂质纳米颗粒对组织转谷氨酰胺酶异构体表达水平的影响

阿尔茨海默病 (AD) 是一种神经退行性疾病，代表了痴呆症的最普遍原因。它还与大脑中异常的淀粉样蛋白-β (Aβ) 蛋白沉积有关。由于氧化应激与 AD 相关，因此抗氧化剂可能在受影响的人的饮食中发挥作用。因此，我们评估了全身给药固体脂质纳米颗粒 (SLN) 以促进姜黄素 (CUR) 递送对野生型 (WT) 和 TgCRND8 (Tg) 小鼠中 TG2 同种型表达水平的影响。使用了表达两个突变的人类淀粉样前体蛋白 (APP) 基因的 AD 实验模型。还进行了行为研究以评估所有治疗诱导的认知表现和记忆功能的改善。Bcl-2、Cyclin-D _{1的表达水平}, 和 caspase-3 切割也进行了评估。在这项研究中，我们首次证明，在 WT 和 Tg 小鼠中全身施用 SLNs-CUR 可以不同地调节 TG2 同种型，这些同种型作用于凋亡途径激活或蛋白质的能力修复 Tg 小鼠大脑中的细胞损伤。在这项研究中，我们还建议 SLNs-CUR 可以成为治疗 AD 的创新工具。