Novel insights into famotidine as a GSK-3ß inhibitor: An explorative study in aluminium chloride-induced Alzheimer's disease rat model.
Behav Brain Res
; 476: 115270, 2024 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-39317263
ABSTRACT
Alzheimer's disease (AD), a chronic neurodegenerative disease, presents a substantial global health challenge. This study explored the potential therapeutic role of famotidine, a histamine (H2) receptor antagonist, as a glycogen synthase kinase-3ß (GSK-3ß) inhibitor in the context of AD induced by aluminium chloride (AlCl3) in a rat model. The intricate relationship between GSK-3ß dysregulation and AD pathogenesis, particularly in amyloid-ß (Aß) production, formed the basis for investigating famotidine's efficacy. Molecular modelling revealed famotidine's efficient binding to GSK-3ß, suggesting inhibitory potential. In behavioural assessments, famotidine-treated groups exhibited dose-dependent improvements in Morris Water Maze, Novel Object Recognition, and Y-Maze tests, comparable to the standard Rivastigmine tartrate group. Biochemical analyses showed that famotidine inhibits acetylcholinesterase, decreases lipid peroxidation, increases antioxidant activity, and mitigates oxidative stress. Moreover, famotidine significantly lowered the levels of GSK-3ß, IL-6, and Aß(1-42). The neuroprotective effects of famotidine were further supported by histopathological analysis. This comprehensive investigation underscores famotidine's potential as a GSK-3ß inhibitor, providing insights into its therapeutic impact on AD induced by AlCl3. The study offers a promising avenue for repurposing famotidine due to its established safety profile and widespread availability, highlighting its potential in addressing the formidable challenge of AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Behav Brain Res
/
Behav. brain res
/
Behavioural brain research
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia
País de publicação:
Holanda