The role of β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD) is still considered crucial. The state of Aβ aggregation is critical in promoting neuronal loss and neuronal function impairment. Recently, we demonstrated that Acetylcholine (ACh) is neuroprotective against the toxic effects of Aβ in the cholinergic LAN-2 cells. In biophysical experiments, ACh promotes the soluble Aβ peptide conformation rather than the aggregation-prone β-sheet conformation. In order to better understand the biological role of ACh in AD, we studied the effect of Aβ 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 Aβ in both undifferentiated and RA-differentiated TB cells. Our results show that TB cells are responsive to Aβ. Moreover, in undifferentiated cells 1 h treatment with Aβ 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 Aβ-treated and non-treated cells after 4 and 7 days in vitro. The RA-differentiated cells are not sensitive to Aβ. In TB cell line ACh is able to blunt the effects of Aβ. The ability of ACh to protect non-cholinergic cells against Aβ reinforces the hypothesis that, in addition to its role in cholinergic transmission, ACh could also act as a neuroprotective agent.

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

POLVERINO, ARIANNA;SORRENTINO, PIERPAOLO;JACINI, FRANCESCA;SORRENTINO, Giuseppe
2017

Abstract

The role of β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD) is still considered crucial. The state of Aβ aggregation is critical in promoting neuronal loss and neuronal function impairment. Recently, we demonstrated that Acetylcholine (ACh) is neuroprotective against the toxic effects of Aβ in the cholinergic LAN-2 cells. In biophysical experiments, ACh promotes the soluble Aβ peptide conformation rather than the aggregation-prone β-sheet conformation. In order to better understand the biological role of ACh in AD, we studied the effect of Aβ 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 Aβ in both undifferentiated and RA-differentiated TB cells. Our results show that TB cells are responsive to Aβ. Moreover, in undifferentiated cells 1 h treatment with Aβ 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 Aβ-treated and non-treated cells after 4 and 7 days in vitro. The RA-differentiated cells are not sensitive to Aβ. In TB cell line ACh is able to blunt the effects of Aβ. The ability of ACh to protect non-cholinergic cells against Aβ reinforces the hypothesis that, in addition to its role in cholinergic transmission, ACh could also act as a neuroprotective agent.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11367/63688
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