Effects of Acetylcholine on β-Amyloid-Induced cPLA2 Activation in the TB Neuroectodermal Cell Line: Implications for the Pathogenesis of Alzheimer’s Disease
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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.
KeywordsAlzheimer’s disease β-Amyloid Phospholipase A2 Acetylcholine TB cell line Differentiation
The authors thank Dr. Maria Teodora Valente and Dr. Luisa Arnese for their helpful technical support during the experiments.
The work was supported by a Grant from MIUR (FIRB–MERIT RBNE08LN4P:006) and University of Naples Parthenope, Naples, Italy.
Authors made substantial contributions to conception and design, acquisition of data, analysis, and interpretation of data. Authors participated in drafting the article or revising it critically and they gave final approval of the version to be submitted. Study conception and design A. Polverino, A.M. D’Ursi, G. Sorrentino; Acquisition of data A. Polverino, M. Grimaldi; Analysis and interpretation of data A. Polverino, M. Grimaldi, P. Sorrentino, F. Jacini, A.M. D’Ursi, G. Sorrentino; Drafting of manuscript A. Polverino, M. Grimaldi, P. Sorrentino, F. Jacini, A.M. D’Ursi, G. Sorrentino; English Quality revision P. Sorrentino; Critical revision G. Sorrentino, A. Polverino.
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Conflict of interest
The authors declare that there is no personal or institutional conflict of interest related to the presented research and its publication.
All procedures performed in studies involving human were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments.
Informed consent was obtained from the relatives of the patient involved in the study.