Neuron loss is a devastating and permanent effect of CNS trauma or disease. Several studies have shown neuroprotective effects of PPARs, most notably PPARγ. For instance, lipid peroxidation was shown to raise PPARγ levels in motor neurons in a model of ALS (Benedusi et al., 2012). This was believed to be a self-protective mechanism since PPARγ activation promotes the expression of lipid detoxifying genes such as lipoprotein lipase and glutathione transferase a-2 (Benedusi et al., 2012). PPARγ also may regulate neuronal responses to ischemia since conditional deletion of PPARγ in neurons increases their susceptibility to ischemia in vitro (Zhao et al., 2009). Further, the PPARγ agonist troglitazone enhances survival of rat motor neurons in culture and PPARγ activation by 15d-PGJ2 protects PC12 cells from nitrosative-induced cell death (Lim et al., 2004). In vivo, activating PPARγ in a middle cerebral artery occlusion model of stroke reduces infarct size and lowers cyclin D1, a protein involved in programmed cell death (Pei et al., 2010). Additionally, PPARγ activation can stabilize mitochondria and protect neurons against apoptotic cell death and oxidative stress by upregulating
