The effect of Aminogluthetimide on Amyloid beta Toxicicity in neuronal cell lines

Alzheimer's disease is an irreversible and progressive neurodegenerative disease, which results in with memory deficit. The increase in amyloid beta (Aβ) concentration is one of initiating factors in the neurodegeneration process. Some steroids have protective effects on cell death induced by toxic agents (such as Aβ peptide) depending on their dose. In-vivo vary steroids may occur by reactions such as cholesterol side cleavage, hydroxylation or aromatization. Aminogluthetimide can inhibit steroid synthesis on the step of side cleavage or aromatization in dose dependent manner. The aim of this study is to determine the effect of aminogluthetimide on Aβ toxicity and also to evaluate the changes of steroid levels including estron, estrodiol, DHEA, DHEA sulfate, androstenedion and pregnenolon sülfat. In our study, the rat feochromacytoma cell line (PC-12) was used as an neuroendocrine model. The effects of Aβ 25-35 peptide which is the functional fragment of Aβ protein, and aminogluthedime on steroid levels were determined by ELISA and LCMS MS methods. MTT reduction method and light microscopy were used to assess cell viability. Aβ treatment during 72 hours reduced cell viability by 50 % of control cells. Aβ induced estron, and androstenedione levels but also decreased estradiol and DHEA levels. Aminogluthedimide partially protected the cells against to Aβ toxicity in dose dependent manner. In our study, it has been shown that Aβ can change the level of steroids in PC-12 cells and also the changes of steroid levels can affect the cell viability. The protective effect of aminogluthetimide may be related to block of cholesterol input for steroid synthesis or it may be connected the inhibition of exitotoxicity induced by Aβ peptide. It needs to be further studies to explain the relationship between aminogluthetimide and receptor modulation in cell.