TY - JOUR
T1 - 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
AU - Camarillo-López, Raúl Horacio
AU - Hernández Rodríguez, Maricarmen
AU - Torres-Ramos, Mónica Adriana
AU - Arciniega-Martínez, Ivonne Maciel
AU - García-Marín, Iohanan Daniel
AU - Correa Basurto, José
AU - Méndez Méndez, Juan Vicente
AU - Rosales-Hernández, Martha Cecilia
PY - 2020/10/29
Y1 - 2020/10/29
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - M4 compound
KW - amyloid beta peptide (Aβ1-42)
KW - astrocyte cells
KW - scopolamine
KW - β-secretase
UR - http://www.scopus.com/inward/record.url?scp=85095399583&partnerID=8YFLogxK
U2 - 10.3390/molecules25215009
DO - 10.3390/molecules25215009
M3 - Artículo
C2 - 33137907
AN - SCOPUS:85095399583
SN - 1420-3049
VL - 25
JO - Molecules (Basel, Switzerland)
JF - Molecules (Basel, Switzerland)
IS - 21
ER -