Akademik Veri Yönetim Sistemi
37th ECNP congress, Milan, İtalya, 20 - 24 Eylül 2024, ss.1-2, (Özet Bildiri)
Alzheimer's disease (AD) is the primary cause of dementia, affecting approximately 45
million people worldwide, accounting for about 60 to 70 percent of all cases [1,2]. The two
main hallmarks of AD pathology are the accumulation of plaques composed of extracellular
amyloid beta (Aβ) protein and neurofibrillary tangles formed by hyperphosphorylated tau
protein. Different acetylcholinesterase inhibitors are being used in the treatment of AD,
leading the way in developing new and promising therapeutic strategies to slow disease
progression and alleviate symptoms. However, the molecular mechanisms underlying the
disease and the signal pathways involved have not yet been identified [4,5]. Thymol is one of
the most important nutrient components of the thyme species, and is a colorless crystalline
monoterpenic phenol. Due to its lipophilic nature, it readily crosses the blood-brain barrier
and exerts effects on the function of ion channels and neurons. Furthermore, it is suggested
that due to its acetylcholinesterase inhibitor activity, it could be a novel therapeutic target for
AD treatment. Thymol has been shown to enhance cognitive activities in dementia models;
however, the precise mechanism underlying this effect remains to be fully unraveled [4,6].
Sodium butyrate (SB) is a histone deacetylase inhibitor and has the ability to support cell
differentiation. The human glioblastoma cell line, U-87, is used to give the cells a cholinergic
neuron character/can differentiate to a cholinergic neural [7].
The aim of our study is to examine the potentialssible neuroprotective effects of Thymol
(Sigma – Aldrich catalog no. T0501) within AD model, generated by Aβ 25-35 (Sigma – Aldrich
catalog no. A4559) after the in vitro U-87 cell was cholinergic neuron characterized by SB
(Stem Cell Technologies catalog no. #72242).
U-87 cells were treated with 2mM SB for 48 [7] hours to demonstrate the acquisition of a
cholinergic neuron character microscopically and at the protein level. CHAT protein
expression, a biomarker for cholinergic neurons, was then assessed using Western blotting.
The cytotoxicity of Aβ 25-35 in U-87 cells was evaluated using the MTT assay at concentrations
ranging from 1μM to 25μM (25μM, 10μM, 5μM, 2.5μM and 1μM).
After determining the Aβ 25-35 IC50 value (1μM), an appropriate concentration was chosen to
establish an AD model. To assess Thymol's potential neuroprotective effect, U-87 cells were
treated with varying concentrations (400μM, 200μM, 100μM, 50μM and 10μM) of Thymol,
and the effects were evaluated using the MTT assay. The Mann-Whitney U test from non-
parametric tests was used to assess the statistically significant difference between the
averages of the groups in experimental findings a significance level of p < 0.05 was chosen
for all statistical analyses.
The Western blot results demonstrated that 2mM SB application significantly increased
CHAT protein levels compared to the control group, indicating the acquisition of cholinergic
neuronal character. It was also observed that microscopically the 2mM SB application
extended the axons of U-87 cells compared to the control group. In the MTT experiment, a
significant proliferation was observed in the AD model, generated by 1μM, calculated at
50.85% while in the 50μM combination with Thymol, calculating the vitality at 88.17%.