Neuroprotection with pioglitazone against LPS insult on dopaminergic neurons may be associated with its inhibition of NF-κB and JNK activation and suppression of COX-2 activity

Increasing evidence links neuroinflammation to Parkinson's disease. Microglia are mediators of neuroinflammation. Overactivation of microglia contributes to the release of cyclooxygenase 2 and prostaglandin E2 during neuronal insults. We have previously shown that pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, inhibits microglia activation, reduces proinflammatory factors, and protects dopaminergic neurons. Here, we demonstrated that pioglitazone protects dopaminergic neurons by inhibiting abnormal microglia activation, interfering with phosphorylation of jun N-terminal kinase and nuclear factor kappa-B, and by suppressing cyclooxygenase 2 expression and the subsequent prostaglandin E2 synthesis. Therefore, the anti-inflammatory properties of pioglitazone may be useful for ameliorating the progression of Parkinson's disease.