N-Stearoyl-L-Tyrosine Inhibits the Senescence of Neural Stem/Progenitor Cells Induced by Aβ1-42 via the CB2 Receptor

Alzheimer's disease, one of the neurodegenerative diseases, shows the progressive senescence of neural progenitor/stem cells. N-Stearoyl-L-tyrosine (NsTyr) showed neuroprotective effect against chronic brain ischemia in previous reports. In the present study, we find the antisenescent effects of NsTyr-2K in NSPCs induced by A beta(1-42) in vitro. Cell viability of NSPCs was evaluated by CCK8 assay; SA-beta-gal staining was used to evaluate senescence of NSPCs. CB receptors were detected by immunohistochemistry in NSPCs. AM251 or AM630 was used to offset the anti-senescence effects afforded by NsTyr-2K. The positive rate of SA-beta-gal staining was significantly increased in NSPCs after incubation with A beta(1-42) for 9 days. CB receptors were found on the surface of NSPCs. The expression level of CB1 receptors was significantly decreased in NSPCs after incubation with A beta(1-42). This phenomenon was reversed dose-dependently by NsTyr-2K. NsTyr-2K attenuated A beta(1-42) induced NSPCs senescence dose-dependently, and its antisenescence effect was completely abolished by AM630. A beta(1-42) dose-dependently increased the prosenescence molecules p16 and Rb. Their expression was inhibited by NsTyr-2K dose-dependently and blocked by AM630 in NSPCs. These results suggest that NsTyr-2K can alleviate the senescence of NSPCs induced by A beta(1-42) via CB2 receptor.