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Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS.
Sunildutt, Naina; Ahmed, Faheem; Chethikkattuveli Salih, Abdul Rahim; Lim, Jong Hwan; Choi, Kyung Hyun.
Afiliação
  • Sunildutt N; Department of Mechatronics Engineering, Jeju National University, Jeju63243, Republic of Korea.
  • Ahmed F; Department of Mechatronics Engineering, Jeju National University, Jeju63243, Republic of Korea.
  • Chethikkattuveli Salih AR; Department of Mechatronics Engineering, Jeju National University, Jeju63243, Republic of Korea.
  • Lim JH; Terasaki Institute for Biomedical InnovationLos Angeles21100, United States.
  • Choi KH; Department of Mechatronics Engineering, Jeju National University, Jeju63243, Republic of Korea.
ACS Omega ; 9(3): 3793-3806, 2024 Jan 23.
Article em En | MEDLINE | ID: mdl-38284068
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper and lower motor neurons, resulting in debilitating muscle weakness and atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges in managing the disease that affects approximately two individuals per 100,000 people annually. To address the urgent need for effective ALS treatments, we conducted a drug repurposing study using a combination of bioinformatics tools and molecular docking techniques. We analyzed sporadic ALS-related genes from the GEO database and identified key signaling pathways involved in sporadic ALS pathogenesis through pathway analysis using DAVID. Subsequently, we utilized the Clue Connectivity Map to identify potential drug candidates and performed molecular docking using AutoDock Vina to evaluate the binding affinity of short-listed drugs to key sporadic ALS-related genes. Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Notably, Lestaurtinib demonstrated high binding affinity toward multiple proteins, suggesting its potential as a broad-spectrum therapeutic agent for sporadic ALS. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: ACS Omega Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: ACS Omega Ano de publicação: 2024 Tipo de documento: Article País de publicação: Estados Unidos