| First Author | Guan PP | Year | 2019 |
| Journal | Neurotherapeutics | Volume | 16 |
| Issue | 4 | Pages | 1255-1268 |
| PubMed ID | 31392591 | Mgi Jnum | J:368408 |
| Mgi Id | MGI:8215240 | Doi | 10.1007/s13311-019-00770-z |
| Citation | Guan PP, et al. (2019) Cyclooxygenase-2 Induced the beta-Amyloid Protein Deposition and Neuronal Apoptosis Via Upregulating the Synthesis of Prostaglandin E(2) and 15-Deoxy-Delta(12,14)-prostaglandin J(2). Neurotherapeutics 16(4):1255-1268 |
| abstractText | Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandins (PGs) have been shown to be involved in the pathogenesis of Alzheimer's disease. Analysis of the underlying mechanisms elucidated a function of sequential PGE(2) and PGD(2) synthesis in regulating beta-amyloid protein (Abeta) deposition by modulating tumor necrosis factor alpha (TNF-alpha)-dependent presenilin (PS)1/2 activity in COX-2 and APP/PS1 crossed mice. Specifically, COX-2 overexpression accelerates the expression of microsomal PGE synthase-1 (mPGES-1) and lipocalin-type prostaglandin D synthase (L-PGDS), leading to the synthesis of PGE(2) and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) in 6-month-old APP/PS1 mice. Consequently, PGE(2) has the ability to increase Abeta production by enhancing the expression of PS1/2 in a TNF-alpha-dependent manner, which accelerates the cognitive decline of COX-2/APP/PS1 mice. More interestingly, low concentrations of 15d-PGJ(2) treatment facilitate the effects of PGE(2) on the deposition of Abeta via TNF-alpha-dependent PS1/2 mechanisms. In contrast, high concentrations of 15d-PGJ(2) treatment inhibit the deposition of Abeta via suppressing the expression of TNF-alpha-dependent PS1/2. In this regard, a high concentration of 15d-PGJ(2) appears to be a therapeutic agent against Alzheimer's disease. However, the high 15d-PGJ(2) concentration treatment induces neuronal apoptosis via increasing the protein levels of Bax, cleaved caspase-3, and DFF45, which further impairs the learning ability of APP/PS1 mice. |
