Post-transcriptional knockdown of BRCC3 via siRNA-loaded niosomes modulates autophagy and endoplasmic reticulum stress in rotenone-induced Parkinson’s Disease model
Articles > Article · 2026
Authors: Çevik GÜREL, EZGİ TUT, GÖKÇE CEREN KUŞCU, AYLİN BUHUR, ÖZGÜN SELİM GERMİYAN, Leila Sabour-Takanlou, Maryam Sabour-Takanlou, CEM GÜLER, Nefise Ülkü KARABAY YAVAŞOĞLU, Fatih OLTULU, Altuğ YAVAŞOĞLU
JOURNAL OF DRUG TARGETING, Journal Indexed in SCI Expanded, International, WoS, 2026, vol 1, pp 1-21
DOI: 10.1080/1061186X.2026.2669781
Summary
Parkinson’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.