Effects of Acetylcholine on beta-Amyloid-Induced cPLA2 Activation in the TB Neuroectodermal Cell Line: Implications for the Pathogenesis of Alzheimer's Disease

The role of beta-amyloid (A beta) in the pathogenesis of Alzheimer's disease (AD) is still considered crucial. The state of A beta aggregation is critical in promoting neuronal loss and neuronal function impairment. Recently, we demonstrated that Acetylcholine (ACh) is neuroprotective against the toxic effects of A beta in the cholinergic LAN-2 cells. In biophysical experiments, ACh promotes the soluble A beta peptide conformation rather than the aggregation-prone beta-sheet conformation. In order to better understand the biological role of ACh in AD, we studied the effect of A beta on the phosphorylation of the cytosolic phospholipase A2 (cPLA2) in the TB neuroectodermal cell line, which differentiates toward a neuronal phenotype when cultured in the presence of retinoic acid (RA). We chose the phosphorylated form of cPLA2 (Ser505, Phospho-cPLA2) as a biomarker to test the influence of ACh on the effects of A beta in both undifferentiated and RA-differentiated TB cells. Our results show that TB cells are responsive to A beta. Moreover, in undifferentiated cells 1 h treatment with A beta induces a 2.5-fold increase of the Phospho-cPLA2 level compared to the control after 24 h in vitro, while no significant difference is observed between A beta-treated and non-treated cells after 4 and 7 days in vitro. The RA-differentiated cells are not sensitive to A beta. In TB cell line ACh is able to blunt the effects of A beta. The ability of ACh to protect non-cholinergic cells against A beta reinforces the hypothesis that, in addition to its role in cholinergic transmission, ACh could also act as a neuroprotective agent.