| First Author | Wang P | Year | 2016 |
| Journal | Aging Cell | Volume | 15 |
| Issue | 5 | Pages | 861-71 |
| PubMed ID | 27240539 | Mgi Jnum | J:236114 |
| Mgi Id | MGI:5804735 | Doi | 10.1111/acel.12495 |
| Citation | Wang P, et al. (2016) Prostaglandin I2 upregulates the expression of anterior pharynx-defective-1alpha and anterior pharynx-defective-1beta in amyloid precursor protein/presenilin 1 transgenic mice. Aging Cell 15(5):861-71 |
| abstractText | Cyclooxygenase-2 (COX-2) has been recently identified to be involved in the pathogenesis of Alzheimer's disease (AD). Yet, the role of an important COX-2 metabolic product, prostaglandin (PG) I2 , in the pathogenesis of AD remains unknown. Using human- and mouse-derived neuronal cells as well as amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice as model systems, we elucidated the mechanism of anterior pharynx-defective (APH)-1alpha and pharynx-defective-1beta induction. In particular, we found that PGI2 production increased during the course of AD development. Then, PGI2 accumulation in neuronal cells activates PKA/CREB and JNK/c-Jun signaling pathways by phosphorylation, which results in APH-1alpha/1beta expression. As PGI2 is an important metabolic by-product of COX-2, its suppression by NS398 treatment decreases the expression of APH-1alpha/1beta in neuronal cells and APP/PS1 mice. More importantly, beta-amyloid protein (Abeta) oligomers in the cerebrospinal fluid (CSF) of APP/PS1 mice are critical for stimulating the expression of APH-1alpha/1beta, which was blocked by NS398 incubation. Finally, the induction of APH-1alpha/1beta was confirmed in the brains of patients with AD. Thus, these findings not only provide novel insights into the mechanism of PGI2 -induced AD progression but also are instrumental for improving clinical therapies to combat AD. |
