THE EFFECTS OF PPAR? AGONISTS ON OXIDATIVE STRESS RELATED PROTEINS IN PARKINSON’S DISEASE MODEL
Project no. 92 · Status: Kapanmış · 2017
Summary
Parkinson's Disease is the second most common movement disorder in the world, 0.1% of the world population and 3% of people over 65 years of age. Although many reasons are emphasized, the reason for the emergence of the disease is not known exactly. Besides, there are studies showing that one of the basic mechanisms that play a role in the emergence and progression of the disease is oxidative stress. In the case of oxidative stress, the transcription factor NF-E2-related factor (Nrf2) is known to bind to the antioxidant response element (ARE), inducing antioxidant and phase2 detoxification enzymes. Our aim in this project is to investigate the effect of peroxisome proliferator-activated receptor gamma (PPAR) agonists on oxidative stress-related proteins and to investigate the molecular mechanisms associated with oxidative stress (Nrf2) in dopaminergic neuronal damage. Within the scope of the project, the effects of pioglitazone and tideglusib on glutathione-related enzyme activity such as GSH and GST, GR were measured using ELISA assays. In addition, the effects of treatments on Nrf2 mRNA and PPAR? protein levels were determined by real-time PCR and Western Blot methods, respectively. Cytotoxicity decreased and antioxidant enzyme activity increased significantly with PPAR? agonist treatments (p<0.05). In addition, decreased Nrf2 mRNA levels in dopaminergic damage has been shown to increase with pioglitazone. These results indicate that both glutathione-related enzymes and Nrf2 pathway are effective in observing receptor-mediated neuroprotection; it supports that receptors play an important role especially in neuronal protection. Key Words: oxidative stress, PPAR?, Parkinson’s Disease, Nrf2-ARE pathway