TLR4 antibody-mediated signaling system in apoptosis of hippocampal neurons

Toll-like receptor 4 (TLR4) antibody, protein kinase B (AKT) inhibitor, LY 294002, and glycogen synthase kinase 3β (GSK-3β) inhibitor, LiCl, were used by Yu He and colleagues from Nantong University, China to attenuate or augment the effects of the TLR4-phosphatidylinositol 3 kinase (PI3K)/AKT-GSK-3β signaling pathway so as to identify the participation of this signaling system in the apoptosis of hippocampal neurons. Their findings showed that the apoptotic ratio of hippocampal neurons stimulated by lipopolysaccharide was significantly higher compared with the control group.

Both the expression of P-AKTSer473 and P-GSK-3βSer9 in hippocampal neurons stimulated by lipopolysaccharide decreased compared with the control, while the level of active Caspase-3 and the ratio of Bax/Bcl-2 were significantly increased. The level of active Caspase-3 and the ratio of Bax/Bcl-2 in hippocampal neurons treated with TLR4 antibody or the GSK-3β inhibitor, LiCl, decreased before intervention with lipopolysaccharide, but increased after treatment with the AKT inhibitor, LY294002. These findings, published in the Neural Regeneration Research (Vol. 8, No. 29, 2013), suggest that the TLR4-PI3K/AKT-GSK3β signaling pathway may be involved in lipopolysaccharide-induced apoptosis of hippocampal neurons. Thus, a new target for treatment of neurodegenerative diseases would be to block apoptosis signaling pathways in vulnerable neurons.