Therapeutic Effects of miR-21-5p–Enriched Milk Extracellular Vesicles on Alzheimer’s Disease–Associated Neurotoxicity in Vitro
Cell Biochemistry and Biophysics, cilt.84, sa.2, ss.2609-2625, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 84 Sayı: 2
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s12013-026-02022-2
- Dergi Adı: Cell Biochemistry and Biophysics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Sayfa Sayıları: ss.2609-2625
- Anahtar Kelimeler: miR-21-5p, Small extracellular vesicles (sEVs), Amyloid beta (A beta), Alzheimer's disease, SH-SY5Y cells
- Uşak Üniversitesi Adresli: Evet
Özet
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 (Aβ)–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. Aβ-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-α 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 Aβ 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.