Neuroprotection with pioglitazone against LPS insult on dopaminergic neurons may be associated with its inhibition of NF-kappaB 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 E(2) 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 E(2) synthesis. Therefore, the anti-inflammatory properties of pioglitazone may be useful for ameliorating the progression of Parkinson's disease.
Xing
Bin
B
University of Kentucky, Chandler Medical Center, Department of Anatomy and Neurobiology, 800 Rose Street, 310 Davis Mills Building, Lexington, KY 40536-0298, USA.
Liu
Mei
M
Bing
Guoying
G
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004660:Encephalitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides; D008636:Mesencephalon / Q000166:cytology; D017628:Microglia / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000077205:Pioglitazone; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D014446:Tyrosine 3-Monooxygenase; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D004298:Dopamine; D000077205:Pioglitazone