MOLECULAR NEUROBIOLOGY, 2025 (SCI-Expanded)
There is still no approved treatment for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by amyloid plaques, neurofibrillary tangles, and synaptic dysfunction. In an in vitro AD model, this study aimed to comparatively assess the neuroprotective effects of the citrus flavonoid Hesperidin and the casein kinase 2 (CK2) inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB) as potential therapeutic targets for AD. First, SH-SY5Y neuroblastoma cells were differentiated into cholinergic neuron-like cells using all-trans retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). Then, to generate an in vitro AD model, 20 mu M A beta(1-42) was applied to induce neurotoxicity in differentiated SH-SY5Y cells. The neuroprotective effects of the CK2 inhibitor DRB and Hesperidin on the in vitro AD model were evaluated using MTT, RT-qPCR, and ELISA methods. Both Hesperidin and DRB, at high concentrations, reduced cell viability in differentiated SH-SY5Y cells for 24 and 48 h (p < 0.05 to p < 0.01). Pre-treatment with Hesperidin at 25 and 50 mu M and DRB at 0.25 and 0.5 mu M for 24 h increased ADAM10 gene expression and decreased BACE1 gene expression, both of which are associated with AD markers, compared to the 20 mu M A beta(1-42) treatment group (p < 0.05). Pre-treatment with the DRB at 0.25 and 0.5