| First Author | Kuroki Y | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 424 |
| Issue | 3 | Pages | 409-13 |
| PubMed ID | 22766501 | Mgi Jnum | J:186243 |
| Mgi Id | MGI:5431256 | Doi | 10.1016/j.bbrc.2012.06.121 |
| Citation | Kuroki Y, et al. (2012) Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of beta-amyloid peptide fragment 31-35. Biochem Biophys Res Commun 424(3):409-13 |
| abstractText | Epidemiological studies have suggested that the long-term use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX) activity moderates the onset or progression of Alzheimer's disease (AD). Thus it has been suggested that prostaglandin E(2) (PGE(2)), a major end-product of COX, may play a pathogenic role in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream from COX, has not been fully elucidated. To examine the involvement in AD pathology of microsomal PGES-1 (mPGES-1), a PGES enzyme, we here prepared primary cerebral neuronal cells from the cerebri of wild-type and mPGES-1-deficient mice and then treated them with beta-amyloid (Abeta) fragment 31-35 (Abeta(31-35)), which represents the shortest sequence of native Abeta peptide required for neurotoxicity. Treatment of wild-type neuronal cells with Abeta(31-35) induced mPGES-1 gene expression and PGE(2) production, followed by significant apoptotic cell death, but apoptosis was not induced in mPGES-1-deficient cells. Furthermore, the combined treatment of Abeta(31-35) and PGE(2) induced apoptosis in mPGES-1-deficient neuronal cells. These results indicated that mPGES-1 is induced during Abeta-mediated neuronal cell death and is involved in Abeta-induced neurotoxicity associated with AD pathology. |
