Mitochondrial dysfunction, oxidative stress, and neuroinflammation play a critical role in the occurrence and progression of Alzheimer's disease (AD). MicroRNAs (miRNAs) have been studied recently as Show more
Mitochondrial dysfunction, oxidative stress, and neuroinflammation play a critical role in the occurrence and progression of Alzheimer's disease (AD). MicroRNAs (miRNAs) have been studied recently as potential therapeutic approaches for AD. In this study, we examined the function and underlying mechanism of microRNA-25802 (miR-25802), a newly discovered miRNA in an AD model. In order to evaluate the levels of oxidative stress, mitochondrial damage and neuroinflammation in neuroblastoma cells, four experimental groups were created: control group (neuroblastoma cells, SH-SY5Y), amyloid beta (Aβ)-induced neuroblastoma cells (SY5Y-Aβ), small extracellular vesicles (sEVs)-only group and miR-25802-loaded small extracellular vesicles (sEV-miR25802) administered group. Neuroinflammation, oxidative stress, mitochondrial damage, tau hyperphosphorylation, and Aβ accumulation were evaluated in Aβ-induced neuroblastoma cells. Oxidative stress was analyzed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase 1 (GPX1). Inflammatory markers such as tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule 1 (ICAM1), and brain-derived neurotrophic factor (BDNF) mRNA levels, a neurotrophic factor, were evaluated by RT-qPCR. Neurofilament light chain (NfL), vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1) and cytochrome c (Cyt-c), mitochondrial transcription factor A (TFAM), PTEN-induced kinase 1 (PINK1) and dynamin-1-like protein (DNM1L) protein levels were determined by ELISA. Mechanistically, sEV-miR25802 were shown to provide anti-inflammatory and neuroprotective effects by regulating neuroinflammation, mitochondrial dysfunction, and oxidative stress. These findings reveal the regulatory role of miR-25802 on neuroinflammation, mitochondrial damage, and oxidative stress and suggest that it may be a potential therapeutic target for AD. Show less
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 cell Show more
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. Show less