Overexpression of cyclooxygenase-2 stimulates amyloid β-peptide production in neuronal cells

Abstract

Alzheimer's disease (AD) is characterized by deposition of amyloid β-peptide (Aβ) derived from amyloid precursor protein (APP). Recent studies suggest that cyclooxygenase (COX)-2 is involved in the progress of AD. However, the mechanistic relationship between COX-2 expression and the neurodegenerative process of AD is unclear. To address this issue, we established neuroblastoma×glioma hybrid NG108-15 cells stably expressing human COX-2. The original cells are devoid of COX-2, but express a low level of COX-1. The COX-2-expressing cells showed three- to fourfold increase in COX activity and prostaglandin E 2 production. Reverse transcription-polymerase chain reaction analysis demonstrated that APP expression was increased by approximately twofold in the COX-2-expressing cells as compared with control cells. The secretion of proteolytic products of APP, Aβ and a secreted form of APP was also increased. A COX inhibitor, indomethacin, suppressed the production of the secreted form of APP and Aβ by inhibition of APP expression. These results suggest that COX-2 is involved in the formation of the amyloid plaques through the increased of Aβ in AD.