Open AccessProstaglandin I 2 upregulates the expression of anterior pharynx‐defective‐1α and anterior pharynx‐defective‐1β in amyloid precursor protein/presenilin 1 transgenic mice
Author(s) -
Wang Pu,
Guan PeiPei,
Guo JingWen,
Cao LongLong,
Xu GuoBiao,
Yu Xin,
Wang Yue,
Wang ZhanYou
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12495
Subject(s) - biology , pharynx , presenilin , genetically modified mouse , amyloid precursor protein , transgene , anatomy , prostaglandin , prostaglandin e2 , microbiology and biotechnology , endocrinology , pathology , gene , biochemistry , alzheimer's disease , medicine , disease
Summary 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 ) I 2 , in the pathogenesis of AD remains unknown. Using human‐ and mouse‐derived neuronal cells as well as amyloid precursor protein/presenilin 1 ( APP / PS 1) transgenic mice as model systems, we elucidated the mechanism of anterior pharynx‐defective ( APH )‐1α and pharynx‐defective‐1β induction. In particular, we found that PGI 2 production increased during the course of AD development. Then, PGI 2 accumulation in neuronal cells activates PKA / CREB and JNK /c‐Jun signaling pathways by phosphorylation, which results in APH ‐1α/1β expression. As PGI 2 is an important metabolic by‐product of COX ‐2, its suppression by NS 398 treatment decreases the expression of APH ‐1α/1β in neuronal cells and APP / PS 1 mice. More importantly, β‐amyloid protein (Aβ) oligomers in the cerebrospinal fluid ( CSF ) of APP / PS 1 mice are critical for stimulating the expression of APH ‐1α/1β, which was blocked by NS 398 incubation. Finally, the induction of APH ‐1α/1β was confirmed in the brains of patients with AD . Thus, these findings not only provide novel insights into the mechanism of PGI 2 ‐induced AD progression but also are instrumental for improving clinical therapies to combat AD .