Alzheimer’s disease (AD) is a neurodegenerative disease with no cure nowadays; there is no treatment either to prevent or to stop its progression. In vitro studies suggested that tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl) carbamate named the M4 compound can act as both β-secretase and an acetylcholinesterase inhibitor, preventing the amyloid beta peptide (Aβ) aggregation and the formation of fibrils (fAβ) from Aβ1-42. This work first aimed to assess in in vitro studies to see whether the death of astrocyte cells promoted by Aβ1-42 could be prevented. Second, our work investigated the ability of the M4 compound to inhibit amyloidogenesis using an in vivo model after scopolamine administration. The results showed that M4 possesses a moderate protective effect in astrocytes against Aβ1-42 due to a reduction in the TNF-α and free radicals observed in cell cultures. In the in vivo studies, however, no significant effect of M4 was observed in comparison with a galantamine model employed in rats, in which case this outcome was attributed to the bioavailability of M4 in the brain of the rats.

中文翻译：

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叔丁基-（4-羟基-3-（（3-（2-甲基哌啶-基）丙基）氨基甲酰基）苯基）氨基甲酸酯对淀粉样蛋白 1-42 刺激的星形胶质细胞和东莨菪碱模型具有中等保护活性

阿尔茨海默病 (AD) 是一种神经退行性疾病，目前无法治愈。没有治疗可以预防或阻止其进展。体外研究表明，名为 M4 化合物的叔丁基-（4-羟基-3-（（3-（2-甲基哌啶-基）丙基）氨基甲酰基）苯基）氨基甲酸酯可作为 β-分泌酶和乙酰胆碱酯酶抑制剂，防止淀粉样蛋白 β 肽 (Aβ) 聚集和从 Aβ1-42 形成原纤维 (fAβ)。这项工作首先旨在评估体外研究，看看是否可以防止 Aβ1-42 促进的星形胶质细胞死亡。其次，我们的工作使用东莨菪碱给药后的体内模型研究了 M4 化合物抑制淀粉样蛋白生成的能力。结果表明，由于细胞培养物中观察到的 TNF-α 和自由基的减少，M4 在星形胶质细胞中对 Aβ1-42 具有中等保护作用。然而，在体内研究中，与用于大鼠的加兰他敏模型相比，没有观察到 M4 的显着影响，在这种情况下，这种结果归因于 M4 在大鼠大脑中的生物利用度。