Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A Comprehensive In Silico, In Vitro, and In Vivo Studies on its Neuroprotective Effects and Molecular Interactions in Parkinson's Disease.

Autor:	Kokabi S; Department of Cell and Molecular Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran., Amiri M; Department of Cell and Molecular Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran., Alahdad N; Department of Cell and Molecular Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran., Yazdanpanah MA; Department of Cell and Molecular Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran., Shahbazi A; Department of Neuroscience, Iran University of Medical Sciences, Tehran, Iran., Barati M; Department of Medical Biotechnology, Iran University of Medical Sciences, Tehran, Iran., Simorgh S; Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran., Azedi F; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran., Angaji SA; Kharazmi University Department of Cell and Molecular Biology, Faculty of Biological Science, Tehran Iran., Tavakol S; Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.; Department of Research and Development, Tavakol BioMimetic Technologies Company, Tehran, Iran.
Jazyk:	angličtina
Zdroj:	Current medicinal chemistry [Curr Med Chem] 2024 Oct 23. Date of Electronic Publication: 2024 Oct 23.
DOI:	10.2174/0109298673329597241006053718
Abstrakt:	Introduction: Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic cells and as of now, there is no established definitive treatment available for this condition. Method: In this study, the focus was on investigating the impact of SVAK-12, a small molecule that can cross the blood-brain barrier and remain stable without structural changes. The effect of SVAK-12 was investigated in vitro on neurotoxicity, in vivo model of Parkinson's Diseases and in silico. Result: Through in vitro and in vivo experiments, as well as molecular docking simulations, it was found that SVAK-12 (375 ng.ml) led to increased cell viability, reduced cellular damage, and decreased production of NO and ROS. Additionally, it boosted levels of important neurotrophic factors like BDNF (130.49%) and GDNF (116.38%), potentially aiding in alleviating motor disability and depression. The study also highlighted SVAK-12's potential as a therapeutic candidate for neurological disorders due to its ability to increase tyrosine hydroxylase expression and dopamine levels (4.84 times). While it did not significantly improve motor symptoms in vivo, it did enhance motor asymmetry in the forelimbs and gene expression related to brain regions. Besides, it induced significant BMP-2 gene expression in substantial nigra regions without significant changes in GDNF and Nurr1 gene expression in the striatum expression. The docking of SVAK-12, Levodopa, Amantadine, Biperiden, Selegiline, and Rasagiline to the binding site of GFRα1, sortilin, and TrkB showed that SVAK-12 had greater MolDock score than Selegiline and Amantadine for GFRα1 and greater than amantadine for Sortilin and TrKB. Conclusion: Overall, the study suggests that SVAK-12's neuro-biocompatibility, ability to reduce free radicals, and enhanced neurotrophic factors make it a promising candidate as a neuroprotective drug. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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