In vitro investigation of miR-206-3p-loaded extracellular vesicles as modulators of Aβ-induced neurodegeneration
Gonullu, Sinan, Aydin, Seyma, Celik, Hamit, Celik, Oguz, Kucukler, Sefa, Topal, Ahmet, Akay, Ramazan, Yildiz, M. Onur, Alim, Bulent, Culha, M. Hudai, Ozdemir, Selcuk
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 (A beta). The sEV-miR-206-3p complexes were successfully loaded with miR-206-3p (similar to 0.001 copies per particle) without disrupting vesicle integrity or inducing cytotoxicity at the optimized concentration of 5 mu g/mL. A beta treatment significantly increased oxidative stress markers (ROS, MDA, LDH) and decreased antioxidant enzyme activity (SOD), while GPX1 showed an opposite trend. Furthermore, A beta elevated proinflammatory gene expression (ICAM1, TNF-alpha) 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 A beta 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 A beta pathology. These findings demonstrate that miR-206-3p-loaded sEVs protect neuroblastoma cells from A beta-induced neurodegenerative processes, highlighting their potential as a novel drug delivery system for neuroprotection.
- Journal
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Year
- 2026
- Volume
- 802
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- DOI
- 10.1016/j.bbrc.2026.153306
- WoS UID
- WOS:001679513900001