Post-transcriptional knockdown of BRCC3 via siRNA-loaded niosomes modulates autophagy and endoplasmic reticulum stress in rotenone-induced Parkinson's Disease model

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dc.authoridhttps://orcid.org/0000-0002-3759-6616
dc.authoridhttps://orcid.org/0000-0003-0266-2115
dc.authoridhttps://orcid.org/0000-0002-6104-175X
dc.authoridhttps://orcid.org/0000-0001-7077-0965
dc.authoridhttps://orcid.org/0000-0002-6361-7150
dc.contributor.authorGürel, Çevik
dc.contributor.authorTut, Ezgi
dc.contributor.authorKuşçu, Gökçe Ceren
dc.contributor.authorBuhur, Aylin
dc.contributor.authorGermiyan, Özgün Selim
dc.contributor.authorLeila Sabour-Takanlou
dc.contributor.authorMaryam Sabour-Takanlou
dc.contributor.authorGüler, Cem
dc.contributor.authorYavaşoğlu, Nefise Ülkü Karabay
dc.contributor.authorOltulu, Fatih
dc.contributor.authorYavaşoğlu, Altuğ
dc.date.accessioned2026-05-08T10:25:50Z
dc.date.available2026-05-08T10:25:50Z
dc.date.issued2026
dc.departmentFakülteler, Diş Hekimliği Fakültesi, Temel Bilimler Bölümü
dc.description.abstractParkinson's Disease (PD) is a prevalent neurodegenerative disorder. Recent studies implicate BRCA1-/BRCA2-containing complex 3 (BRCC3) in PD-related mechanisms such as ubiquitin-proteasome system dysfunction. This study aimed to evaluate the therapeutic potential of BRCC3 silencing via systemically administered siRNA-loaded niosomes in a rotenone-induced rat model of PD. Niosomes were synthesised by thin-film hydration, and three BRCC3-targeted siRNA sequences were tested in primary midbrain dopaminergic neurons. The most effective sequence, identified by Real-Time Quantitative PCR (RT-qPCR) and immunofluorescence, was used for in vivo studies. The PD model was induced in adult male rats (n = 24/group) by subcutaneous rotenone administration (2 mg/kg/day) for 35 days. In the in vivo phase of the study, behavioural, biochemical, in vivo imaging (IVIS), histological, and RT-qPCR analyses were performed. IVIS analysis confirmed brain accumulation of niosome-siRNA complexes within 3-5 h. Complementary analyses demonstrated that siRNA treatment significantly enhanced locomotor performance, restored redox homeostasis and dopamine levels, attenuated neuronal loss, upregulated autophagy-related proteins (↑LC3-II, ↑Beclin), suppressed endoplasmic reticulum stress markers (↓GRP78/Bip, ↓CHOP), elevated tyrosine hydroxylase expression, and reduced α-synuclein accumulation. In conclusion, siRNA-mediated suppression of BRCC3 via siRNA-loaded niosomes provides neuroprotection by modulating autophagy, ER stress, and antioxidant pathways, supporting BRCC3 as a promising therapeutic target for PD.
dc.identifier.citationÇevik Gürel, Tut, E., Kuşçu, G. C., Buhur, A., Germiyan, Ö. S., Sabour-Takanlou, L., Sabour-Takanlou, M., Güler, C., Karabay Yavaşoğlu, N. Ü., Oltulu, F., & Yavaşoğlu, A. (2026). Post-transcriptional knockdown of BRCC3 via siRNA-loaded niosomes modulates autophagy and endoplasmic reticulum stress in rotenone-induced Parkinson's disease model. Journal of Drug Targeting. Advance online publication. https://doi.org/10.1080/1061186X.2026.2669781
dc.identifier.doi10.1080/1061186X.2026.2669781
dc.identifier.pmid42090613
dc.identifier.urihttps://hdl.handle.net/20.500.12941/412
dc.indekslendigikaynakPubMed
dc.institutionauthorBuhur, Aylin
dc.institutionauthoridhttps://orcid.org/0000-0002-3759-6616
dc.language.isoen
dc.relation.ispartofJournal of Drug Targeting
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAutophagy
dc.subjectBRCC3
dc.subjectParkinson’s Disease
dc.subjectEndoplasmic Reticulum Stress
dc.subjectGene Silencing
dc.subjectNiosome
dc.titlePost-transcriptional knockdown of BRCC3 via siRNA-loaded niosomes modulates autophagy and endoplasmic reticulum stress in rotenone-induced Parkinson's Disease model
dc.typeArticle

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