Neuroprotective Effects of Hesperidin and CK2 Inhibitor DRB on A?1-42-Induced Neurotoxicity in Differentiated SH-SY5Y Cells

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dc.authorid0000-0001-6473-5813
dc.authorid0000-0002-3555-3946
dc.contributor.authorEciroglu-Sarban, Hamiyet
dc.contributor.authorAltin-Celik, Pinar
dc.contributor.authorKelicen-Ugur, Pelin
dc.contributor.authorDonmez-Altuntas, Hamiyet
dc.date.accessioned2026-01-24T12:31:00Z
dc.date.available2026-01-24T12:31:00Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractThere 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 M concentrations for 24 h decreased CK2 alpha gene expression in the in vitro AD model compared to the 20 mu M A beta(1-42) treatment group (p < 0.05), whereas Hesperidin had no effect (p > 0.05). Both pre-treatment with Hesperidin and DRB significantly decreased A beta(1-42) levels (p < 0.01), p-Tau (T181) levels (p < 0.05), and the Bax/Bcl-2 ratio (p < 0.05). As a result, our study showed that both Hesperidin and DRB inhibited A beta production by suppressing the amyloidogenic pathway and activating the non-amyloidogenic pathway while also exerting an inhibitory effect on neuronal apoptosis. CK2 may be a potential therapeutic target and could contribute to the pathophysiology of AD. However, these findings should be validated by further studies.
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBITAK); Erciyes University Scientific Research Projects Coordination Unit [TDK-2020-10151]
dc.description.sponsorshipOpen access funding provided by the Scientific and Technological Research Council of Turkiye (TUBITAK). This work was financially supported by the Erciyes University Scientific Research Projects Coordination Unit (No. TDK-2020-10151).
dc.identifier.doi10.1007/s12035-025-05082-2
dc.identifier.endpage12735
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.issue10
dc.identifier.pmid40445481
dc.identifier.scopus2-s2.0-105006927071
dc.identifier.scopusqualityQ1
dc.identifier.startpage12722
dc.identifier.urihttps://doi.org/10.1007/s12035-025-05082-2
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5581
dc.identifier.volume62
dc.identifier.wosWOS:001499553600001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Neurobiology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20260121
dc.subjectAlzheimer's disease
dc.subjectCK2
dc.subjectDRB
dc.subjectHesperidin
dc.subjectNeuronal differentiation
dc.subjectSH-SY5Y neuroblastoma cells
dc.titleNeuroprotective Effects of Hesperidin and CK2 Inhibitor DRB on A?1-42-Induced Neurotoxicity in Differentiated SH-SY5Y Cells
dc.typeArticle

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