Tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl)carbamate Has Moderated Protective Activity in Astrocytes Stimulated with Amyloid Beta 1-42 and in a Scopolamine Model

叔丁基-(4-羟基-3-((3-(2-甲基哌啶基)丙基)氨基甲酰基)苯基)氨基甲酸酯在受淀粉样蛋白 β 1-42 刺激的星形胶质细胞和东莨菪碱模型中具有调节保护活性

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作者:Raúl Horacio Camarillo-López, Maricarmen Hernández Rodríguez, Mónica Adriana Torres-Ramos, Ivonne Maciel Arciniega-Martínez, Iohanan Daniel García-Marín, José Correa Basurto, Juan Vicente Méndez Méndez, Martha Cecilia Rosales-Hernández

Abstract

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.

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