Identifying RAGE inhibitors as potential therapeutics for Alzheimer’s disease via integrated in-silico approaches

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26220%2F26%3A0198011" target="_blank" >RIV/00216305:26220/26:0198011 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-025-01271-0" target="_blank" >https://www.nature.com/articles/s41598-025-01271-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-025-01271-0" target="_blank" >10.1038/s41598-025-01271-0</a>

Result language

angličtina

Original language name

Identifying RAGE inhibitors as potential therapeutics for Alzheimer’s disease via integrated in-silico approaches

Original language description

Alzheimer’s disease is a neurodegenerative disorder characterized by two hallmarks: amyloid beta plaques and neurofibrillary tangles. The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor involved in the pathophysiology of various diseases including cancer, diabetes, cardiovascular diseases, and Alzheimer’s disease (AD). Therefore, targeting RAGE could be an effective strategy to block RAGE signaling pathways. The present study aims to identify potential RAGE inhibitors against AD through comprehensive in-silico approaches. A total of 708,580 compounds were screened from numerous databases using structure-based virtual screening and ADMET evaluation. Further, the molecules with good glide scores were assessed by molecular docking studies. Subsequently, the top six ligands were subjected to molecular dynamic (MD) simulations for 100 ns and binding free energy calculations to check their stability with RAGE (PDB: 6XQ3). The per-residue decomposition analysis revealed that specific residues namely, GLY_20, ALA_21, LYS_39, GLU_50, LYS_52, ARG_98, GLN_100, LYS_110, ASN_112, and ARG_198 played a key role in the binding process. Furthermore, the trajectory analysis (DCCM and PCA) analyzed the dominant motions of residues and predicted the stability of protein-ligand complexes. In conclusion, the Hit-6 compound could be a promising candidate for targeting RAGE and deserves further consideration as an anti-Alzheimer drug.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30401 - Health-related biotechnology

Project

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Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2025

Confidentiality

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

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

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Volume of the periodical

15

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

1-17

UT code for WoS article

001502759100002

EID of the result in the Scopus database

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