Repurposing major metabolites of lamiaceae family as potential inhibitors of alpha-synuclein aggregation to alleviate neurodegenerative diseases: an in silico approach

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60460709%3A41110%2F25%3A102405" target="_blank" >RIV/60460709:41110/25:102405 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60460709:41210/25:102405 RIV/60460709:41340/25:102405

Výsledek na webu

<a href="https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1519145/full" target="_blank" >https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1519145/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2025.1519145" target="_blank" >10.3389/fphar.2025.1519145</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Repurposing major metabolites of lamiaceae family as potential inhibitors of alpha-synuclein aggregation to alleviate neurodegenerative diseases: an in silico approach

Popis výsledku v původním jazyce

Neurodegenerative disorders (NDs) are typically characterized by progressive loss of neuronal function and the deposition of misfolded proteins in the brain and peripheral organs. They are molecularly classified based on the specific proteins involved, underscoring the critical role of protein-processing systems in their pathogenesis. Alpha-synuclein (alpha-syn) is a neural protein that is crucial in initiating and progressing various NDs by directly or indirectly regulating other ND-associated proteins. Therefore, reducing the alpha-syn aggregation can be an excellent option for combating ND initiation and progression. This study presents an in silico phytochemical-based approach for discovering novel neuroprotective agents from bioactive compounds of the Lamiaceae family, highlighting the potential of computational methods such as functional networking, pathway enrichment analysis, molecular docking, and simulation in therapeutic discovery. Functional network and enrichment pathway analysis established the direct or indirect involvement of alpha-syn in various NDs. Furthermore, molecular docking interaction and simulation studies were conducted to screen 85 major bioactive compounds of the Lamiaceae family against the alpha-syn aggregation. The results showed that five compounds (alpha-copaene, gamma-eudesmol, carnosol, cedryl acetate, and spathulenol) had a high binding affinity towards alpha-syn with potential inhibitory activity towards its aggregation. MD simulations validated the stability of the molecular interactions determined by molecular docking. In addition, in silico pharmacokinetic analysis underscores their potential as promising drug candidates, demonstrating excellent blood-brain barrier (BBB) permeability, bioactivity, and reduced toxicity. In summary, this study identifies the most suitable compounds for targeting the alpha-syn aggregation and recommends these compounds as potential therapeutic agents against various NDs, pending further in vitro and in vivo validation.

Název v anglickém jazyce

Repurposing major metabolites of lamiaceae family as potential inhibitors of alpha-synuclein aggregation to alleviate neurodegenerative diseases: an in silico approach

Popis výsledku anglicky

Neurodegenerative disorders (NDs) are typically characterized by progressive loss of neuronal function and the deposition of misfolded proteins in the brain and peripheral organs. They are molecularly classified based on the specific proteins involved, underscoring the critical role of protein-processing systems in their pathogenesis. Alpha-synuclein (alpha-syn) is a neural protein that is crucial in initiating and progressing various NDs by directly or indirectly regulating other ND-associated proteins. Therefore, reducing the alpha-syn aggregation can be an excellent option for combating ND initiation and progression. This study presents an in silico phytochemical-based approach for discovering novel neuroprotective agents from bioactive compounds of the Lamiaceae family, highlighting the potential of computational methods such as functional networking, pathway enrichment analysis, molecular docking, and simulation in therapeutic discovery. Functional network and enrichment pathway analysis established the direct or indirect involvement of alpha-syn in various NDs. Furthermore, molecular docking interaction and simulation studies were conducted to screen 85 major bioactive compounds of the Lamiaceae family against the alpha-syn aggregation. The results showed that five compounds (alpha-copaene, gamma-eudesmol, carnosol, cedryl acetate, and spathulenol) had a high binding affinity towards alpha-syn with potential inhibitory activity towards its aggregation. MD simulations validated the stability of the molecular interactions determined by molecular docking. In addition, in silico pharmacokinetic analysis underscores their potential as promising drug candidates, demonstrating excellent blood-brain barrier (BBB) permeability, bioactivity, and reduced toxicity. In summary, this study identifies the most suitable compounds for targeting the alpha-syn aggregation and recommends these compounds as potential therapeutic agents against various NDs, pending further in vitro and in vivo validation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

1663-9812

Svazek periodika

16

Číslo periodika v rámci svazku

APR 16 2025

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

19

Strana od-do

—

Kód UT WoS článku

001478747300001

EID výsledku v databázi Scopus

2-s2.0-105004028069