关键词: 虾青素, 阿尔茨海默病, 线粒体自噬, NOD样受体蛋白家族成员X1, 核因子E2相关因子2

Abstract: Objective To explore the effects of glutamate on mitophagy and apoptosis in HT22 cells and evaluate the protective effects and molecular mechanisms of astaxanthin pretreatment．Methods HT22 cells were treated with glutamate and astaxanthin．The effects on mitophagy were assessed using Western Blot and PCR．Results Glutamate treatment significantly inhibited primary mitophagy（PINK1,Parkin,pULK1^ser555 and LC3II）and secondary mitophagy（LAMP1 and Rab7）while upregulating cleaved Caspase-3 expression．Astaxanthin pretreatment notably reduced apoptosis and restored mitophagy,the expression levels of PINK1,Parkin,pULK1^Ser555 and LC3II were significantly upregulated（by 2.3-fold,2.6-fold,83.3% and 81.1% respectively,P<0.05）,but this effect was blocked by the autophagy inhibitor BafA1．Additionally,glutamate suppressed Nrf2 nuclear translocation and NLRX1 expression,whereas astaxanthin promoted Nrf2 nuclear translocation and increased NLRX1 expression by 25.8% and 33.2%,respectively．Bioinformatics analysis revealed three Nrf2 binding sites in the NLRX1 promoter region,suggesting that Nrf2 may regulate NLRX1 transcriptional activity．Conclusions The study demonstrates that astaxanthin exhibited potential neuroprotective effect by activating mitophagy through the Nrf2/NLRX1 pathway．

Key words: astaxanthin, Alzheimer's disease, mitophagy, NLRX1, Nrf2