Lipopolysaccharide stimulates the secretion of the amyloid precursor protein via a protein kinase C-mediated pathway

• Main Authors: Claire I. Small, Geoffrey A. Lyles, Kieran C. Breen
• Format: Article
• Language: English
• Published: Elsevier 2005-08-01
• Series: Neurobiology of Disease
• Subjects: Alzheimer; Amyloid; Lipopolysaccharide; Glia; Protein kinase C
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996105000318
• ISSN: 1095-953X

The processing of the amyloid precursor protein (APP) by the secretase family of protease enzymes can be influenced by a variety of diverse factors, including elements of the immune response. In this study, we have investigated the effect of the pro-inflammatory lipopolysaccharide (LPS) on APP processing in rat glial cell cultures derived from both cortex and cerebellum. LPS activation of the cells, as monitored by the induction of the pro-inflammatory nitric oxide synthase (iNOS) enzyme, elicited no change in the overall cellular expression levels of APP, although there was a marked concentration-related increase in the secretion of the soluble APPs following both short- (4 h) and long-term (18 h) drug treatment times. The stimulation of APPs secretion was blocked by the protein kinase C (PKC) inhibitor GF109203x, suggesting that LPS may act via a PKC-mediated pathway to increase APPs secretion.