Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Eritoran attenuates neurotoxicity via apoptosis and TLR signaling pathways and modulates T cell responses in Alzheimer’s disease model

Articles in Press

Document Type : Original Article

Authors
Canan Eroğlu Güneş 1
Ebru Nur Dursun 1
Fatma Seçer Çelik 2
Sedef Akçaalan 3
Ercan Kurar 1
1 Department of Medical Biology, Faculty of Medicine, Necmettin Erbakan University, Konya, Türkiye
2 Department of Medical Biology and Genetics, Faculty of Medicine, Ankara Medipol University, Ankara, Türkiye
3 Department of Molecular Biology and Genetics, Faculty of Science, Necmettin Erbakan University, Konya, Türkiye
10.22038/ijbms.2026.96158.20735
Abstract
Objective(s): Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, and neuronal loss. Toll-like receptor (TLR)-mediated neuroinflammation plays an important role in AD pathogenesis by triggering inflammatory responses. This study investigated the neuroprotective effects of eritoran, a TLR4 antagonist, and its role in modulating T-cell responses in an in vitro AD model.
Materials and Methods: SH-SY5Y cells were differentiated into cholinergic neurons and exposed to Aβ to establish an in vitro AD model. The model was validated by measuring p-Tau, α-synuclein, Aβ, and acetylcholinesterase (AChE) levels. Cell viability was assessed using a CCK-8 assay. Apoptosis and TLR pathway gene expression were analyzed by qRT-PCR. In addition to apoptosis-related protein levels, ELISA was used to evaluate IL2, IL4, and IFN-γ concentrations in Jurkat T cells treated with conditioned media.
Results: In the AD model, p-Tau, α-synuclein, Aβ, and AChE levels increased significantly. Eritoran pretreatment significantly reduced these pathological markers. Eritoran pretreatment significantly down-regulated apoptosis-related genes (BAX, CASP3, CASP7, CYCS, CASP8, CASP9, FADD, FAS and P53) and up-regulated anti-apoptotic BCL2. Protein levels of CASP7, BAX, and CYCS were also reduced. Additionally, TLR signaling pathway genes (TLR1–5, TLR7, TLR9, TLR10, and MYD88) were significantly down-regulated. Furthermore, eritoran up-regulated IL2 and IL4 while decreasing IFN-γ levels in T cells.
Conclusion: Eritoran demonstrated neuroprotective effects in an in vitro AD model and modulated T-cell cytokine responses. These findings support further investigation of eritoran as a candidate for AD-related research.
Keywords
Alzheimer’s disease
Apoptosis
Eritoran
Neuroinflammatory-diseases
Neuroprotective agents
T-Lymphocytes
Toll-Like receptor
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 10 November 2026