15-Deoxy-Δ12,14-prostaglandin J2, a specific ligand for peroxisome proliferator-activated receptor-γ, induces neuronal apoptosis

Although considerable research has shown a role for peroxisome proliferator-activated receptors (PPAR) in adipose differentiation and in the regulation of inflammation, little is known about its possible functions in neurons. We investigated the role of PPAR gamma in primary cultures of cortical neurons 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 degeneration and nuclear condensation that were consistent with neurons dying by apoptosis. The morphological changes associated with incubation of cortical neurons with 15d-PGJ(2) were prevented following pretreatment of neurons with the general caspase inhibitor, Z-VAD. These results highlight a novel role for PPAR gamma in neurons and suggest that unwarranted activation of PPAR gamma may contribute to the neuronal apoptosis associated with certain neurodegenerative disorders including Alzheimer's disease (AD). NeuroReport 12:839-843 (C) 2001 Lippincott Williams & Wilkins.