| Abstrakt: |
Objective: Alpha-synuclein (-syn), is a cytosolic protein, involved in functions such as synaptic function, neuronal plasticity, learning, development, phosphorylation, cellular differentiation, and regulation of dopamine uptake. α-syn toxicity affects synaptic vesicles, ER, Golgi, lysosomes and nucleus, and disrupts interorganelle communications. Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-syn protein. Recent studies have shown that α-syn can localize in the nucleus of different cell types, bind to nuclear DNA, regulate histone modification and affect the expression of many genes. Based on this information, we aim to investigate whether α-syn pathology we created by overexpressing SNCA affects the genes that encode general transcription factors(TFs) rather than directly regulating gene expression. Methods: In our study, PD-like pathology was established with overexpression of α-syn in the HEK293T cell line. Treatments were carried out at 48, 72 and 96 hours. TFs potentially associated with α-syn were determined using the TRRUSTv2 database, and the effect of α-syn on the mRNA expression levels of selected transcription factors (JUN,RELA HMGA1,TP53, SMAD3) was investigated using the qRTPCR technique. Experiments were repeated 3 times independently of each other. In GraphPad InStat DTCG3.06 software, the data distribution was statistically evaluated first with oneway ANOVA followed by Tukey-Kramer multiple comparison test or first with Kruskal Wallis and then with Dunn's multiple comparison test, depending on whether it was normal or not. Results: According to our results, the mRNA expression of JUN, HMGA1 significantly decreased in SNCA group (the group with α-syn overexpression) compared to control, while the RELA expression increased (p<0.01, p<0.01, p<0.01, respectively). Our findings also show alteration of the expression of TP53 and SMAD3. Conclusions: These results suggest that α-syn can alter the expression of general TFs and thus play a role in regulating the expression of many genes regulated by general TFs. [ABSTRACT FROM AUTHOR] |
