title: N-Stearoyl-L-Tyrosine Inhibits the Senescence of Neural Stem/Progenitor Cells Induced by Aβ 1-42 via the CB2 Receptor.
abstract: 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 Aβ 1-42 in vitro. Cell viability of NSPCs was evaluated by CCK8 assay; SA-β-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-β-gal staining was significantly increased in NSPCs after incubation with Aβ 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 Aβ 1-42. This phenomenon was reversed dose-dependently by NsTyr-2K. NsTyr-2K attenuated Aβ 1-42 induced NSPCs senescence dose-dependently, and its antisenescence effect was completely abolished by AM630. Aβ 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 Aβ 1-42 via CB2 receptor.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ze-Jian
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
authors.affiliation: Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu