A newly synthesized fibrate derivative reduces oxidative stress and inhibits apoptosis occurrence in CTX-TNA2 rat astrocytes cell line treated with a PPARgamma antagonist.

The worldwide increase in aging population is associated with increasing prevalence of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Peroxisome proliferator-activated receptors (PPARs) are ligand-modulated transcriptional factors belonging to the nuclear hormone receptor superfamily which regulate peroxisosome proliferation as well as other metabolic activities, such as insulin sensitivity, glucose homeostasis, and fatty acid oxidation. PPAR-gamma is the most extensively studied among the three PPAR isoforms and many studies have recently demonstrated the neuroprotective effects of PPAR-gamma agonists in a variety of preclinical models of neurological disorders. In the present study CTX-TNA2 rat astrocytes cell line were treated with G3335 PPAR-gamma antagonist to simulate a neurological disorder. The ability of newly synthesized PPAR-gamma agonists to restore the catalase activity and to revert the oxidative stress induction and apoptosis occurrence were evaluated. Among four different compounds, GL516, a fibrate derivative, showed low cytotoxicity and was proven to be effective in restoring catalase activity, reducing reactive oxygen species (ROS) production and decreasing the apoptosis occurrence triggered by the treatment with G3335. The effects of this molecule appear comparable to the reference compound rosiglitazone especially at prolonged exposure times (96h). The results suggest a role for GL516 in the pathophysiology of neurodegenerative disorders.