Assessing the performance of Coenzyme Q10 loaded DQAsomes to treat Leigh syndrome caused by NDUFS4 knockout

Basit Öğe Kaydı
dc.authorscopusid57302092900
dc.authorscopusid57396839700
dc.authorscopusid57283760100
dc.authorscopusid38862146000
dc.authorscopusid37018154500
dc.contributor.authorUner B.
dc.contributor.authorErgin A.D.
dc.contributor.authorCelik A.
dc.contributor.authorKhatik R.
dc.contributor.authorDwivedi P.
dc.date.accessioned2024-06-12T10:25:02Z
dc.date.available2024-06-12T10:25:02Z
dc.date.issued2024
dc.description.abstractHomozygous mutations in the NDUFS4 gene result in one of the many autosomal recessive forms of Leigh syndrome (LS), which impairs mitochondrial complex I function. In time, this disorder results in mental and motor impairment, often resulting in death. LS has no cure, and treatment focuses on symptom management. The delivery of CoQ10 can be improved in treating LS when caused by mutations in the NDUFS4 gene. Its poor solubility and bioavailability limit its clinical use as a preventative for oxidative damage and mitochondrial function. In this study, we developed CoQ10-loaded DQAsomes, utilizing dequalinium chloride -a bolalipid known for its antimicrobial properties to improve mitochondrial delivery of CoQ10. These DQAsomes were evaluated in an NDUFS4 knockout mouse model. Mitochondria from lung tissue of 32 knock-out mice and matched controls were isolated and CoQ10 uptake was quantified using fluorescence microscopy. Mitochondrial proteins were measured through ELISA, Western Blot, and PCR, and histopathological examination was performed to support the findings. The DQAsomes were measured to be approximately 151.3 nm with a polydispersity index (PDI) of 0.181, and mitochondrial uptake was found to be around 91.2 %. The apoptosis score measured following pure-CoQ10 administration was found to be 5.5 times higher compared to DQAsomes, while the inflammation score measured following DQAsomes administration was found to be 6.2 times lower than pure-CoQ10. Overall, these findings suggest promising therapeutic potential for DQAsomes in LS management, emphasizing their role in targeted mitochondrial CoQ10 delivery and potential clinical application. © 2024en_US
dc.description.sponsorshipSchool of Medicine, Washington University in St. Louis, WUSM; Trakya Üniversitesi; Ankara Universitesien_US
dc.description.sponsorshipWe have collaborated on this project among the Washington University School of Medicine in St. Louis, the University of Health Science and Pharmacy in St. Louis, Trakya University, and Ankara University to accomplish this research. As a result of their assistance, this research has been able to be completed successfully.en_US
dc.identifier.doi10.1016/j.jddst.2024.105809
dc.identifier.issn1773-2247
dc.identifier.scopus2-s2.0-85193971281en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.jddst.2024.105809
dc.identifier.urihttps://hdl.handle.net/20.500.14551/16165
dc.identifier.volume97en_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherEditions de Santeen_US
dc.relation.ispartofJournal of Drug Delivery Science and Technologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectCoenzyme Q10; Dequalinium Chloride; Knockout Mice; Leigh Disease; Mitochondrial Targetingen_US
dc.subjectDequalinium; Mitochondrial Protein; Reduced Nicotinamide Adenine Dinucleotide Dehydrogenase (Ubiquinone); Ubidecarenone; Animal Experiment; Animal Model; Animal Tissue; Antimicrobial Activity; Apoptosis; Article; Controlled Study; Dispersity; Enzyme Linked Immunosorbent Assay; Fluorescence Microscopy; Histopathology; Human; Inflammation; Knockout Mouse; Leigh Disease; Lung Parenchyma; Male; Mitochondrion; Motor Dysfunction; Mouse; Nonhuman; Western Blottingen_US
dc.titleAssessing the performance of Coenzyme Q10 loaded DQAsomes to treat Leigh syndrome caused by NDUFS4 knockouten_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

Scopus İndeksli Yayınlar Koleksiyonu