Akademik Veri Yönetim Sistemi
CELL BIOCHEMISTRY AND BIOPHYSICS, 2026 (SCI-Expanded, Scopus)
Progressive neuronal degeneration linked to oxidative stress, mitochondrial malfunction, and persistent neuroinflammation are the hallmarks of Alzheimer's disease (AD). The current study investigated the neuroprotective potential of miR-21-5p-loaded milk-derived small extracellular vesicles (sEV_miR-21-5p) against amyloid beta (A(3)-induced toxicity in SH-SY5Y neuroblastoma cells. Milk-derived sEVs were isolated and characterized following the MISEV 2018 guidelines, and miR-21-5p was actively loaded into the vesicles. A(3-induced oxidative stress was effectively reduced by treatment with sEV_miR-21-5p, as evidenced by decreased levels of ROS, MDA, LDH, and GPX1, along with restored SOD activity. Furthermore, sEV_miR-21-5p mitigated mitochondrial dysfunction, indicated by increased TFAM expression and decreased Cyt-c, PINK1, and DNM1L levels. The treatment also downregulated inflammation-associated signaling molecules (TNF-alpha and ICAM1) while enhancing BDNF expression, suggesting modulation of neuronal stress-response and survival pathways. In addition, miR-21-5p delivery normalized neuronal cytoskeletal and stress-related protein (NfL), preserved synaptic protein expression (CPLX2 and SMOC1), and significantly reduced tau hyperphosphorylation and A(3 accumulation. These findings demonstrate that milk-derived sEVs serve as efficient, biocompatible carriers for miR-21-5p, enabling targeted delivery and functional recovery in neuronal cells. Taken together, this study underscores the therapeutic potential of sEV_miR-21-5p as a biocompatible and scalable platform for targeted intervention in AD.