Phosphatidylcholine protects neurons from toxic effects of amyloid beta-protein in culture

摘要

Amyloid beta-protein (A beta) is the major component of extracellular plaques in the brains of patients with Alzheimer's disease. It has been suggested that the interaction of A beta with membrane cholesterol is essential for A beta to exert neurotoxicity; however, the effect of phospholipids, another major membrane lipid component, on A beta-induced neurotoxicity remains unclarified. Here we report the protective effect of phosphatidylcholine (PC) on primary cultured neurons against A beta 1-42-induced damage. A beta 1-42 caused neuronal death as demonstrated by lactose dehydrogenase (LDH) release, which was completely prevented by a pretreatment with PC in a dose-dependent manner. PC containing unsaturated long-chain acyl groups, 1,2-dioleoyl-PC (DOPC), also prevented neuronal death caused by A beta 1-42. The oleic acid ethyl-ester (OAEE) partially prevented A beta 1-42-induced neurotoxicity. Neurons that were pretreated with DOPC or OAEE for 24 h, washed out, and exposed to A beta 1-42 in the absence of either of these reagents, were still resistant to A beta 1-42-induced neurotoxicity. In contrast, treatment with phosphotidylserine (PS) or docosahexaenoic acid etyl-ester (DHAEE) had no protective effect on neurons against A beta 1-42-induced damage. These results suggest that the control of cellular PC content, not PS content, may prove useful in the prevention or treatment of Alzheimer's disease. (C) 2016 Elsevier B.V. All rights reserved.