15-Deoxy-Delta(12,14)-prostaglandin J(2), a specific ligand for peroxisomeproliferator-activated receptor-gamma, induces neuronal apoptosis

Although considerable research has shown a role for peroxisome proliferator -activated receptors (PPAR) in adipose differentiation and in the regulatio n of inflammation, little is known about its possible functions in neurons. We investigated the role of PPAR gamma in primary cultures of cortical neu rons and human neuroblastoma SH-SY5Y cells. Incubation of cortical neurons with the specific PPAR gamma ligand 15-Deoxy-Delta (12,14)-prostaglandin J( 2) (15d-PGJ(2)) induced morphological changes including neurite degeneratio n and nuclear condensation that were consistent with neurons dying by apopt osis. The morphological changes associated with incubation of cortical neur ons with 15d-PGJ(2) were prevented following pretreatment of neurons with t he general caspase inhibitor, Z-VAD. These results highlight a novel role f or PPAR gamma in neurons and suggest that unwarranted activation of PPAR ga mma may contribute to the neuronal apoptosis associated with certain neurod egenerative disorders including Alzheimer's disease (AD). NeuroReport 12:83 9-843 (C) 2001 Lippincott Williams & Wilkins.