In vitro investigation of miR-206-3p-loaded extracellular vesicles as modulators of Aβ-induced neurodegeneration

Gönüllü S., AYDIN Ş., Çelik H., Çelik O., KÜÇÜKLER S., TOPAL A., ...Daha Fazla

Biochemical and Biophysical Research Communications, cilt.802, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 802
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.bbrc.2026.153306
  • Dergi Adı: Biochemical and Biophysical Research Communications
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE
  • Anahtar Kelimeler: Alzheimer's disease, Extracellular vesicles, miR-206-3p, Mitochondrial dysfunction, Neuroinflammation, Oxidative stress
  • Atatürk Üniversitesi Adresli: Evet

Özet

In this study, we investigated the therapeutic potential of miR-206-3p delivered via small extracellular vesicles (sEVs) in an in vitro Alzheimer's disease model using SH-SY5Y human neuroblastoma cells treated with amyloid beta (Aβ). The sEV–miR-206-3p complexes were successfully loaded with miR-206-3p (∼0.001 copies per particle) without disrupting vesicle integrity or inducing cytotoxicity at the optimized concentration of 5 μg/mL. Aβ treatment significantly increased oxidative stress markers (ROS, MDA, LDH) and decreased antioxidant enzyme activity (SOD), while GPX1 showed an opposite trend. Furthermore, Aβ elevated proinflammatory gene expression (ICAM1, TNF-α) and reduced neuroprotective BDNF levels, induced mitochondrial dysfunction (increased Cyt-c, PINK1, DNM1L; decreased TFAM), impaired synaptic proteins (CPLX2, ROR1), and promoted tau phosphorylation and Aβ accumulation. Treatment with sEV–miR-206-3p effectively mitigated these alterations, reducing oxidative stress, suppressing neuroinflammatory responses, restoring mitochondrial function and synaptic protein levels, and attenuating tau and Aβ pathology. These findings demonstrate that miR-206-3p-loaded sEVs protect neuroblastoma cells from Aβ-induced neurodegenerative processes, highlighting their potential as a novel drug delivery system for neuroprotection.