Decoding the Puzzle: Understanding How Donepezil Treats Alzheimer’s Disease

Published on April 9, 2022

Imagine trying to solve a complex puzzle with multiple pieces that fit together perfectly. That’s what scientists did in this study on the mechanism of donepezil in treating Alzheimer’s disease (AD). Using network pharmacology and molecular docking, they collected compounds and targets associated with donepezil from various databases. They then created an interactive network that revealed the intricate relationship between the drug and its targets. Through enrichment analyses, they unveiled the functions and mechanisms by which donepezil operates. The study identified key targets and signaling pathways involved in chemical synaptic transmission and cell proliferation, differentiation, and survival. These findings highlight the multi-component, multi-target, and multi-pathway nature of donepezil’s therapeutic effects. This research offers promising insights into how donepezil can help in the treatment of AD.

ObjectiveIn order to explore and further understand the efficacy of donepezil (DNP) in the treatment of Alzheimer’s disease (AD), this research was conducted based on network pharmacology and molecular docking.MethodCompounds of DNP and its effective targets were collected using the TCMSP Chinese medicine system pharmacology database. Disease targets were screened and selected utilizing GeneCards, TTD, DrugBank, CTD, and other online databases. Then, Venn diagrams were generated to identify the intersections. A diseases-drug-active ingredient-key target protein interaction (PPI) network was constructed using the STING database. GO and KEGG enrichment analyses were conducted to predict the function and mechanism of DNP, which were visualized by graphs and bubble charts. After the screening, the top five interacting targets in the PPI network and the compound containing the most active target were selected for molecular docking.ResultsThe study received 110 potential targeting genes and 155 signaling pathways. A strong association between DNP and modulation of chemical synaptic transmission and the regulation of trans-synaptic signaling is noted. Signaling pathways related to the proliferation, differentiation, and survival of cells are also found positively relative. The results revealed that the mechanism of its therapeutic effect is multi-component, multi-target, and multi-pathway, laying a foundation for the follow-up in-depth study of the mechanism of DNP in the treatment of AD.ConclusionThis research provides a superior prediction that AD could be treated using DNP which targets the key proteins and essential pathways associated with the recovery of AD.

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