Therapeutic approach with a novel PPAR α/γ dual agonist in Parkinson’s disease

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and anticipate to be a promising therapeutic target for several neurodegenerative disease including Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. PPARs plays an important roles on the major causes of neurodegenerative disorders such as mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation. In the present study, we evaluated neuroprotective effects of PPAR α/γ dual agonist on the MPTP-induced PD mouse model. Pretreatment of PPAR α/γ dual agonist attenuated MPTP-induced dopaminergic neuronal loss and motor dysfunction. MPTP-induced glial activation was alleviated by pretreatment of PPAR α/γ dual agonist in nigrostriatal pathway. PPAR α/γ dual agonist also prevent MPP + -induced neuronal cell death and ROS generation in in vitro PD model. MPP + -inducedastroglialactivationreducedbyPPAR α/γ dual agonist via suppressing NF-κB signaling in primary astrocytes. Taken together, the present study suggest that PPAR α/γ dual agonist could be useful agent for therapeutic candidates for PD and other neurodegenerative diseases associated with neuroinflammation.