S24795 Inhibit Aβ Aggregation via Upregulation of Endogenous Cryab in Astrocytes

Abstract: The aim of this study was to investigate the possible mechanism of S24795 on amyloid β (Aβ) aggregation via activation α7 nicotinic receptors (α7 nAChRs) as well as upregulation of endogenous αB-crystallin (Cryab). Primary astrocytes were separated from neonatal SD rat cerebral cortex and cultured in vitro. Aβ1-42 oligomers were prepared in vitro. Astrocytes were divided  into  different  groups  and  treated with drugs. The protein levels of Cryab， phosphorylated-Akt and Aβ oligomers in the cells were detected by Western blot. Our results showed that S24795 could significantly increase the protein level of endogenous Cryab in astrocytes. The effect of upregulation of endogenous Cryab by S24795 was significantly inhibited by α7 nAChR antagonist-MLA. After PI3K signaling pathway was blocked by LY294002， the effect of upregulation of endogenous Cryab by S24795 was significantly inhibited. S24795 could significantly increase phosphorylated-Akt in astrocytes. The effect of upregulation of phosphorylated-Akt by S24795 was significantly inhibited by α7 nAChRs antagonist-MLA. After PI3K signaling pathway was blocked by LY294002， the effect of upregulation of phosphorylated-Akt by S24795 was significantly inhibited. In cell lysate and medium， S24795 could significantly enhance astrocyte to inhibit Aβ aggregation. After PI3K signaling pathway was blocked by LY294002， the effect of inhibition Aβ aggregation by S24795 was significantly inhibited. Together， these data indicated that S24795 could significantly inhibit Aβ aggregation via activation α7 nAChRs as well as upregulation of endogenous Cryab in astrocytes. PI3K signaling pathway was likely to be involved in this process. These results provided experimental data in the study of possible mechanism by which S24795 inhibits Aβ aggregation.

CSTR: 32200.14.cjcb.2016.10.0008