N-stearoyltyrosine protects primary neurons from Aβ-induced apoptosis through modulating mitogen-activated protein kinase activity

N-stearoyltyrosine (NsTyr), an anandamide (AEA) analogue is similar to AEA not only structurally but also in terms of biological activity. Since Aβ-induced neuronal injury triggers the activation of mitogen-activated protein kinase (MAPK) pathways and the induction or activation of pro- and anti-apoptotic proteins, in the present study we aimed to assess the protective effect of NsTyr against Aβ induced neuronal apoptosis. Cell viability and neuronal injury were respectively measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay. Hoechst staining and flow cytometric assessment were used to evaluate cell apoptosis. The anti-apoptotic mechanism involved MAPK phosphoryation and Bcl-2/Bax expression was investigated. The best neuroprotective effect on Aβ25-35-induced neuronal apoptosis was observed in the presence of NsTyr (1 μM). NsTyr exerted anti-apoptotic effect at least partly via activating p-ERK-Bcl-2 but suppressing p-p38-Bax pathways. Moreover a dynamic balance between p-ERK and p-p38 MAPK pathways in NsTyr-induced neuronal protection suggested an interaction between them. Our results indicated the neuroprotective effect of NsTyr on Aβ25-35-induced neuronal injury was at least partly due to anti-apoptosis and raised the possibility that NsTyr might reduce neurodegenerative disorders.