1-(7-Chloroquinolin-4-yl)-N-(4-Methoxybenzyl)-5-Methyl-1H-1,2, 3-Triazole-4- carboxamide Reduces Aβ Formation and Tau Phosphorylation in Cellular Models of Alzheimer's Disease.
Amyloid beta
BACE
Kinases
Multi-target
Neuronal cells
Tau phosphorylation
Journal
Neurochemical research
ISSN: 1573-6903
Titre abrégé: Neurochem Res
Pays: United States
ID NLM: 7613461
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
received:
08
09
2021
accepted:
18
12
2021
revised:
17
11
2021
pubmed:
16
2
2022
medline:
1
4
2022
entrez:
15
2
2022
Statut:
ppublish
Résumé
1-(7-Chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4- carboxamide (QTC-4-MeOBnE) is a new multi-target directed ligand (MTDL) rationally designed to have affinity with β-secretase (BACE), Glycogen Synthase Kinase 3β (GSK3β) and acetylcholinesterase, which are considered promising targets on the development of disease-modifying therapies against Alzheimer's Disease (AD). Previously, QTC-4-MeOBnE treatment showed beneficial effects in preclinical AD-like models by influencing in vivo neurogenesis, oxidative and inflammatory pathways. However, the biological effect and mechanism of action exerted by QTC-4-MeOBnE in AD cellular models have not been elucidated yet. Hereby we investigate the acute effect of QTC-4-MeOBnE on neuronal cells overexpressing Amyloid Protein Precursor (APP) or human tau protein, the two main features of the AD pathophysiology. When compared to the control group, QTC-4-MeOBnE treatment prevented amyloid beta (Aβ) formation through the downregulation of APP and BACE levels in APPswe-expressing cells. Furthermore, in N2a cells overexpressing human tau, QTC-4-MeOBnE reduced the levels of phosphorylated forms of tau via the modulation of the GSK3β pathway. Taken together, our findings provide new insights into the mechanism of action exerted by QTC-4-MeOBnE in AD cellular models, and further support its potential as an interesting therapeutic strategy against AD.
Identifiants
pubmed: 35165799
doi: 10.1007/s11064-021-03514-8
pii: 10.1007/s11064-021-03514-8
doi:
Substances chimiques
Amyloid beta-Peptides
0
Amyloid beta-Protein Precursor
0
QTC-4-MeOBnE
0
Quinolines
0
Triazoles
0
tau Proteins
0
Glycogen Synthase Kinase 3 beta
EC 2.7.11.1
Acetylcholinesterase
EC 3.1.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1110-1122Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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