Computational drug repurposing in Parkinson’s disease: Omaveloxolone and cyproheptadine as promising therapeutic candidates

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

Background: Parkinson's disease (PD), a prevalent and progressive neurodegenerative disorder, currently lacks effective satisfactory pharmacological treatments. Computational drug repurposing represents promising efficient strategy for discovery, aiming to identify new therapeutic indications existing pharmaceuticals. Methods: We employed drug-target network approach computationally repurpose FDA-approved drugs from databases such as DrugBank. A literature review was conducted select candidates not previously reported pharmacoprotective against PD. Subsequent in vitro evaluation utilized Cell Counting Kit-8 (CCK8) assays assess the neuroprotective effects of selected compounds SH-SY5Y cell model induced by 1-methyl-4-phenylpyridinium (MPP+). Furthermore, an vivo mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) developed investigate mechanisms action potential identified candidates. Results: Our 176 candidates, with 28 their anti-Parkinsonian lack prior PD-related reporting. CCK8 showed significant neuroprotection cells Omaveloxolone Cyproheptadine. In MPTP-induced model, Cyproheptadine inhibited interleukin-6 (IL-6) expression prevented Tyrosine Hydroxylase (TH) downregulation via MAPK/NFκB pathway, while alleviated TH downregulation, potentially through Kelch-like ECH-associated protein 1 (KEAP1)-NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. Both preserved dopaminergic neurons improved neurological deficits PD model. Conclusion: This study elucidates treatment application computational repurposing, thereby underscoring its efficacy discovery strategy.

Language: Английский

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Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Language: Английский

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Periodic Solutions for a Modified Disease Mathematical Model

Deleted Journal, Journal Year: 2024, Volume and Issue: 31(3), P. 53 - 62

Published: July 26, 2024

The present paper investigates the existence of periodic oscillations for a delayed Parkinson's disease mathematical model. We extend result in literature from stability to oscillation. Two sufficient conditions guarantee oscillation solutions are provided. Some parameter that affects is sensitive our simulation.

Language: Английский

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