Effect of metformin on regulation of cytoskeletal elements in a rotenoneinduced in vitro model of parkinson's disease

Title: Effect of metformin on regulation of cytoskeletal elements in a rotenone-ınduced ın vitro model of Parkinson's disease Aim: In some neurodegenerative diseases such as Parkinson's disease, cytoskeletal elements in the cell cytosol are rearranged. Sirtuin (SIRT) family genes have been shown to be associated with neurodegenerative diseases. Metformin is a direct SIRT1-activating compound. Levodopa, which shows its effect by converting to dopamine in the brain, is used to relieve symptoms in Parkinson's disease. In this study, it is aimed to reveal whether metformin has a positive effect on the stabilization of cytoskeletal elements and the aggregates formed, and to compare it with the effect of levodopa. Method: In this study, a Parkinson's disease model was created with rotenone in the SH-SY5Y cell line. The IC50 value of the substances applied to the cells was determined and the experiments were continued with the appropriate concentration. Metformin, levodopa, and a combination of the two were administered, followed by disease model formation in RA-differentiated and undifferentiated cells. Cell proliferation and viability were determined. Cofilin, CRMP2, SIRT1, NFL, RhoA, alpha-synuclein, TAU, ROCK2 expressions were determined in cDNAs using Real Time PCR method by RNA isolation. The protein levels of cofilin, ROCK2, alpha synuclein, TAU, NFL and CRMP2 were determined by using the ELISA method. Results: In disease models created with ROT, a decrease in gene expression levels of alpha synuclein (p<0.05), cofilin (p<0.01), ROCK2 was observed as a result of administration of metformin and levodopa to cells. It was determined that there was a decrease in protein levels, alpha synuclein and NFL measured as a result of administration of metformin to disease groups. Conclusion: It was observed that the administration of metformin in cells in the Parkinson's disease model had a positive effect on some genes and proteins, but did not cause any changes on some genes and proteins. According to the results obtained, the Rho-ROCK pathway and alpha synuclein are the two key points of the cytoskeleton and Parkinson's disease, and their importance was emphasized in this study.