Mitochondrial Dynamics‑Related Gene Regulation by Epigenetic Suppression of GCN5 Exerts Neuroprotective Effects in Rotenone‑Induced Parkinson’s Disease Model

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dc.authoridhttps://orcid.org/0000-0003-1750-8209
dc.authoridhttps://orcid.org/0000-0002-6104-175X
dc.authoridhttps://orcid.org/0000-0003-0266-2115
dc.authoridhttps://orcid.org/0000-0002-3759-6616
dc.authoridhttps://orcid.org/0000-0001-7077-0965
dc.authoridhttps://orcid.org/0000-0001-8251-4520
dc.authoridhttps://orcid.org/0000-0003-4945-4794
dc.authoridhttps://orcid.org/0000-0002-0525-9690
dc.authoridhttps://orcid.org/0000-0002-7483-0184
dc.authoridhttps://orcid.org/0000-0003-4227-1637
dc.contributor.authorKuşçu, Gökçe Ceren
dc.contributor.authorTut, Ezgi
dc.contributor.authorGürel, Çevik
dc.contributor.authorBuhur, Aylin
dc.contributor.authorGermiyan, Özgün Selim
dc.contributor.authorAvcı, Çığır Biray
dc.contributor.authorGüler, Cem
dc.contributor.authorŞancı, Ebru
dc.contributor.authorYavaşoğlu, Nefise Ülkü Karabay
dc.contributor.authorYavaşoğlu, Altuğ
dc.date.accessioned2026-01-26T10:48:55Z
dc.date.available2026-01-26T10:48:55Z
dc.date.issued2026
dc.departmentFakülteler, Diş Hekimliği Fakültesi, Temel Bilimler Bölümü
dc.description.abstractParkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and mitochondrial dysfunction. Recent studies implicate the histone acetyltransferase GCN5 in regulating mitochondrial homeostasis and oxidative stress. This study investigated the therapeutic potential of GCN5 silencing via systemically administered siRNA-loaded niosomes in a rotenone-induced rat model of PD. Niosomes were prepared using the thin-film hydration method, and the most effective siRNA sequence was selected through real time quantitative PCR (RT-qPCR) and immunofluorescence in primary mesencephalic neurons. Adult male rats were divided into four groups (n=24/group), and PD was induced with rotenone (2 mg/kg/day, s.c., for 35 days). Behavioral assessments, biochemical analyses, IVIS imaging, histopathology, immunohistochemistry, and RT-qPCR were conducted. IVIS confirmed brain accumulation of siRNA– niosomes within 3–5 h post-injection. GCN5 siRNA treatment significantly improved locomotor activity (p<0.05), decreased MDA levels (p<0.05), and restored SOD and dopamine levels (p<0.05). Molecular findings showed decreased GCN5 and mitochondrial fission-related gene Drp-1 expression, increased expression of mitophagy and biogenesis markers (↑Parkin, ↑PINK1, ↑Mfn2, ↑PGC-1α), elevated TH expression, and reduced α-synuclein accumulation. Histological analysis revealed preserved midbrain cytoarchitecture and reduced neuronal damage. In conclusion, these findings highlight that epigenetic silencing of GCN5 via siRNA-loaded niosomal delivery provides neuroprotection in PD by modulating the expression of genes involved in mitochondrial dynamics, offering preclinical support for its development as a novel therapeutic strategy.
dc.identifier.citationKuşçu, G. C., Tut, E., Gürel, Ç., Buhur, A., Germiyan, Ö. S., Avcı, Ç. B., Güler, C., Şancı, E., Karabay Yavaşoğlu, N. Ü., & Yavaşoğlu, A. (2026). Mitochondrial dynamics–related gene regulation by epigenetic suppression of GCN5 exerts neuroprotective effects in rotenone-induced Parkinson’s disease model. Molecular Neurobiology, 63(1), 383–? https://doi.org/10.1007/s12035-026-05700-7
dc.identifier.doi10.1007/s12035-026-05700-7
dc.identifier.issue63
dc.identifier.pmid41565897
dc.identifier.urihttps://hdl.handle.net/20.500.12941/373
dc.indekslendigikaynakPubMed
dc.institutionauthorBuhur, Aylin
dc.institutionauthoridhttps://orcid.org/0000-0002-3759-6616
dc.language.isoen
dc.relation.ispartofMolecular Neurobiology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGCN5
dc.subjectMitochondrial Dynamics
dc.subjectNiosome
dc.subjectParkinson’s Disease
dc.subjectSiRNA Delivery
dc.titleMitochondrial Dynamics‑Related Gene Regulation by Epigenetic Suppression of GCN5 Exerts Neuroprotective Effects in Rotenone‑Induced Parkinson’s Disease Model
dc.typeArticle

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