PEGylated phospholipid nanomicelles protect Swedish mutants APP695 and sweΔ9 N2a mouse neuroblastoma cells from β‐amyloid induced apoptosis

Abstract

The purpose of this study was to determine whether β‐amyloid evokes cell death in Swedish mutants APP695 and sweΔ9 mouse N2a neuroblastoma cells and, if so, whether sterically stabilized phospholipid nanomicelles (SSM) inhibit this process. Mouse N2a neuroblastoma cells stably expressing Swedish mutant APP695 and exon‐9 deletion mutant PS1 (sweΔ9) (2 × 103cells/well) were incubated in the absence or presence of SSM (10–100 μM) overnight. Thereafter, LDH release from and caspase3/7 activity in these cells were determined. We found that β‐amyloid had no significant effects on LDH release from N2a cells either in the absence or presence of SSM (n=3; p>0.5). By contrast, exposure to β‐amyloid was associated with significantly higher caspase 3/7 activity in comparison to control that was significantly attenuated in the presence of SSM in a concentration‐dependent fashion (n=3; p<0.05). Collectively, these data indicate that SSM protect Swedish mutants APP695 and sweΔ9 N2a mouse neuroblastoma cells from β‐amyloid induced apoptosis. W e suggest that SSM should be further developed as a novel nanomedicine for Alzheimer's disease.Supported by IDPH # 73280001, NIH RO1 5R01CA121797, AG024026, VA merit Review and was conducted in a facility supported from NIH RFIP 06RR15482.Ashwini S. Pai is a recipient of Deans Scholar Award UIC 2007–2008 and American Foundation For Aging research (AFAR) fellowship 2007–2008.