Alzheimer disease, one of the neurodegenerative diseases, shows the progressive senescence of neural stem/progenitor cells (NSPCs) in the brain.N-stearoyl-L-tyrosine (NsTyr), a derived compound from N-fatty-acyl amino acids, showed neuroprotective effect against chronic cerebral ischemia.In the present study, we report the effects of NsTyr on the senescence of NSPCs in vitro.The viability was significantly decreased and the positive rate of SA-β-gal staining was increased in NSPCs after incubation with 1 iμmol· L-1 of Aβ42 for 2 weeks, and meanwhile phosphorylation of mTOR decreased correspondently.NsTyr (0.3-3 mol·L-1) attenuated Aβ42 induced NSPCs senescence dose-dependently.AM251 (1 mol·L-1; an antagonist of CB1 cannabinoid receptor) or AM630 (1 mol·L-1 ; CB2 antagonist of cannabinoid receptor) was used to offset the anti-senescence effects afforded by NsTyr.The anti-senescence effect of NsTyr was completely abolished by AM630.NsTyr dose-dependently increased the expression of CB1 and CB2 receptor after 2 w incubation.NsTyr also dose-dependently increased the expression of phosphorylation of mTOR.These results suggest that NsTyr may be effective against the senescence of NSPCs caused by the hostile microenvironment in brain.Its anti-senescence effect may be mainly mediated by CB2 receptor.