Effect of inhibiting disintegrin metalloproteinase 10 on apoptosis of Alzheimer disease APPswe695 cells and its mechanism

Wang Yuxin; He Jing; Zhang Wei; Zhang Xu; Wang Rong

doi:10.3969/j.issn.1009-6574.2025.03.008

Abstract：Objective To investigate the effect of inhibiting A Disintegrin and Metalloproteinase 10(ADAM10)on apoptosis of Alzheimer's disease APPswe695 cells,a model of Alzheimer's disease,and to explore its underlying mechanism.Methods APPswe695 cells were treated with the ADAM10 inhibitor GI254023X at concentrations of 1,5,10,and 20 μmol/L,with PBS and Dimethyl sulfoxide(DMSO)serving as blank and negative controls,respectively.Cell viability was assessed using the Cell Counting Kit-8(CCK-8)assay,and protein expression levels of the serine/threonine kinase(Akt)/forkhead box protein O3a(FOXO3a)signaling pathway and apoptosis-related proteins were measured by Western blot.Results The total protein expression levels of serine/threonine protein kinase(Akt)and Forkhead Box O3a(FOXO3a)in the GI254023X group were(0.973 0±0.157 7)and(1.149 8±0.196 7),respectively,showing no significant differences compared to the PBS and DMSO groups(P＞0.05).However,the ratio of p-FOXO3a(S253)/FOXO3a after 24 h of treatment with 10 μmol/L GI254023X was(0.866 7±0.075 8),significantly lower than those of the PBS(1.000 0±0.000 0)and DMSO(1.016 2±0.050 6)groups(P＜0.05).Conversely,the ratio of p-Akt(S473)/Akt after 24 h of treatment with 10 μmol/L GI254023X was(1.180 6±0.150 2),significantly higher than those of the PBS(1.000 0±0.000 0)and DMSO(0.893 2±0.041 3)groups(P＜0.05).Additionally,GI254023X significantly reduced the expression of the anti-apoptotic protein B-cell lymphoma-2(Bcl-2)(P＜0.05)and significantly increased the expression of the pro-apoptotic proteins caspase-3,caspase-9,and Bcl-2-associated X protein(Bax)(P＜0.05).Conclusions Treatment of APPswe695 cells with 10 μmol/L ADAM10 inhibitor GI254023X significantly inhibited cell viability and induced apoptosis of APPswe695 cells through the Akt/FOXO3a signaling pathway.