Determination of Potential Lead Compound from Magnolia officinalis for Alzheimer's Disease through Pharmacokinetic Prediction, Molecular Docking, Dynamic Simulation, and Experimental Validation.

ABSTRACT: Amyloid β protein (Aβ) deposition has been implicated as the molecular driver of Alzheimer's disease (AD) progression. The modulation of the formation of abnormal aggregates and their post-translational modification is strongly suggested as the most effective approach to anti-AD. Beta-site APP-cleaving enzyme 1 (BACE1) acts upstream in amyloidogenic processing to generate Aβ, which rapidly aggregates alone or in combination with acetylcholinesterase (AChE) to form fibrils. Accumulated Aβ promotes BACE1 activation via glycogen synthase kinase-3β (GSK-3β) and is post-translationally modified by glutaminyl cyclase (QC), resulting in increased neurotoxicity. A novel multi-target inhibitor as a potential AD agent was identified using an in silico approach and experimental validation. Magnoli

SUBMITTER: Youn K 

PROVIDER: S-EPMC11477134 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature