Metal-Medıated Oxıdatıve Stress-Induced Model Of Alzheımer’s Dısease In Human Neuroblastoma Cells
Abstract
Alzheimer’s disease is the most common cause of dementia and is a progressive neurodegenerative disorder. Identifying the factors causing diseases is important but, the etiology of Alzheimer’s disease has not been understood due to the presence of multiple factors causing disease and difficulties in creating experimental models. Oxidative stress is effective amyloid-beta accumulation and metal ions accumulate in Alzheimer’s brain. In the literature; there are in vitro models in which amyloid-beta and metal ions are directly applied to undifferentiated cells, and models established with genetically modified amyloid-beta secreting cells influenced by metal ions. However, these models reflect late-stage pathology. Oxidative stress is effective in the early and late pathogenesis of disease and in this thesis, we aimed to create an in vitro oxidative stress-induced model of Alzheimer’s. For this purpose, human neuroblastoma cells and differentiated cells by retinoic acid to improve neuronal properties of cells have been used. Copper sulphate has been used as oxidative stress inducer and MTT, ELISA and determination of ROS methods have been performed. In conclusion, 50-200 micromolar copper sulphate treatments were decreased cell viability, were increased concentration of amiloid-beta42 and levels of ROS in undifferentiated and differentiated cells compared to control. It has been determined that the model established with differentiated cells represents neuronal characteristics and Alzheimer’s pathology forcefully compared to undifferentiated cells. For the first time in this study; the results demonstrate that copper-mediated oxidative stress- induced model established with differentiated SH-SY5Y by retinoic acid is a useful and effective model for Alzheimer’s disease researches.
