Camarillo-Lopez_2020_Molecules_25_

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 beta-secretase and an acetylcholinesterase inhibitor, preventing the amyloid beta peptide (Abeta) aggregation and the formation of fibrils (fAbeta) from Abeta(1-42). This work first aimed to assess in in vitro studies to see whether the death of astrocyte cells promoted by Abeta(1-42) 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 Abeta(1-42) due to a reduction in the TNF-alpha 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.